LPS-induced premature osteocyte senescence: Implications in inflammatory alveolar bone loss and periodontal disease pathogenesis
Open accessAbstract
Cellular senescence is associated with inflammation and extracellular matrix tissue remodeling through the secretion of proteins termed the senescence-associated secretory phenotype (SASP). Although osteocyte senescence in older individuals in the skeleton is well recognized, whether young alveolar osteocytes can also become senescent is unknown. This is potentially important in the context of periodontal disease, which is an inflammatory condition caused by a gradual change from symbiotic to pathogenic oral microflora that can lead to tooth loss. Our aim was to identify whether senescent osteocytes accumulate in young alveolar bone and whether bacterial-derived lipopolysaccharide (LPS) can influence cellular senescence in alveolar bone. An osteocyte-enriched cell population isolated from alveolar bone expressed increased levels of the known senescence marker p16 Ink4a, as well as select SASP markers known to be implicated alveolar bone resorption (Icam1, Il6, Il17, Mmp13 and Tnfα), compared to ramus control cells. Increased senescence of alveolar bone osteocytes was also observed in vivo using the senescence-associated distension of satellites (SADS) assay and increased γH2AX, a marker of DNA damage associated with senescent cells. To approximate a bacterial infection in vitro, alveolar osteocytes were treated with LPS. We found increased expression of various senescence and SASP markers, increased γH2AX staining, increased SA-β-Gal activity and the redistribution of F-actin leading to a larger and flattened cell morphology, all hallmarks of cellular senescence. In conclusion, our data suggests a model whereby bacterial-derived LPS stimulates premature alveolar osteocyte senescence, which in combination with the resultant SASP, could potentially contribute to the onset of alveolar bone loss.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
γH2AX+ BMAds are substantially increased in both AD mice and old mice compared to their respective controls.
“Immunofluorescence using the DNA damage marker γH2AX, a robust marker of senescent cells50–52, also revealed a substantial increase in γH2AX+ BMAds in both AD mice (Fig. 3q,r) and old mice (Fig. 3s,t) compared with their respective controls.”
From Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis (2025) · cites this paper as [50]
The citation is attached to the description of γH2AX as a marker, not to the citing paper’s reported increase in γH2AX+ BMAds. The Results section identifies γH2AX as a recognized marker of DNA damage and examines it alongside senescence markers in osteocytes, but does not establish it as a robust marker of senescent cells. It does not report the AD- or old-mouse BMAd comparisons. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477 · cited 1× · see citing works
“3) and measured F-actin redistribution and SA-β-gal activity, two additional hallmarks of the cellular senescent program [36, 37].”
BackgroundThe senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206 · cited 1× · see citing works
“A key senescent cell feature is the secretion of a complex mixture of pro-inflammatory cytokines and proteases, known as the senescenceassociated secretory phenotype (SASP) [8].”
BackgroundPeriodontitis: from microbial immune subversion to systemic inflammation
Hajishengallis, G. (2015) · Nature Reviews Immunology · doi:10.1038/nri3785 · Cited by 3,046 · cited 1× · see citing works
“Transition from health to disease in the periodontium is associated with a gradual change from a symbiotic to a pathogenic host-microbial relationship [3, 4].”
BackgroundAging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · cited 1× · see citing works
“In addition to replicative senescence, which is associated with aging phenotypes, stressinduced senescence is also observed following persistent DNA damage resulting from oncogenic or oxidative stress [6, 7].”
BackgroundCellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818 · cited 1× · see citing works
“On the other hand, in agreement with the role of SASP factors in promoting tissue remodeling [9, 44], Mmp13 was consistently upregulated.”
Bonewald, L. F. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.320 · Cited by 2,287 · cited 1× · see citing works
“Osteocytes are the most abundant bone cells and crucial orchestrators of bone remodeling and mineral homeostasis [19], and because of their increased lifespan compared to other bone cells, they are more susceptible to accumulate molecular damage over time [20].”
BackgroundSenescence and aging: Causes, consequences, and therapeutic avenues
McHugh, D., & Gil, J. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201708092 · Cited by 1,233 · cited 1× · see citing works
“In contrast to this beneficial effect in tissue repair, senescent cells increasingly accumulate with aging and are frequently present at sites of age-related pathologies [10].”
BackgroundTargeting cellular senescence prevents age-related bone loss in mice
Farr, J. N., Xu, M., Weivoda, M. M., Monroe, D. G., Fraser, D. G., Onken, J. L., Negley, B. A., Sfeir, J. G., Ogrodnik, M. B., Hachfeld, C. M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4385 · Cited by 1,182 · cited 1× · see citing works
“Since senescent osteocytes in the murine skeleton usually do not appear until ~18 months of age [23, 32], it was curious that a significant 30% of osteocytes from young, 6 month-old alveolar bone exhibit senescent qualities, as evidenced by SADS (Fig.”
BackgroundSelf-citationFat tissue, aging, and cellular senescence
Tchkonia, T., Morbeck, D. E., Von Zglinicki, T., Van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M. D., & Kirkland, J. L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00608.x · Cited by 1,094 · cited 2× · see citing works
“Since premature senescence in young animals has also been observed in the context of inflammation associated with obesity [11, 12], we propose that a similar phenomenon is occurring in young alveolar bone, triggered by bacterial-derived LPS-induced genotoxicity, and constitutes a new paradigm in periodontal bone loss.”
BackgroundSelf-citationA crucial role for adipose tissue p53 in the regulation of insulin resistance
Minamino, T., Orimo, M., Shimizu, I., Kunieda, T., Yokoyama, M., Ito, T., Nojima, A., Nabetani, A., Oike, Y., Matsubara, H., et al. (2009) · Nature Medicine · doi:10.1038/nm.2014 · Cited by 891 · see citing works
Porphyromonas gingivalis: An Overview of Periodontopathic Pathogen below the Gum Line
How, K. Y., Song, K. P., & Chan, K. G. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00053 · Cited by 858 · cited 1× · see citing works
“In order to invade, survive and multiply in the host’s periodontal tissues, gramnegative bacteria utilize a panel of virulence factors as inflammatory mediators [14].”
BackgroundA senescent cell bystander effect: senescence‐induced senescence
Nelson, G., Wordsworth, J., Wang, C., Jurk, D., Lawless, C., Martin‐Ruiz, C., & von Zglinicki, T. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00795.x · Cited by 755 · cited 1× · see citing works
“This premise is reinforced when considering that pro-inflammatory cytokines and matrixdegrading enzymes secreted by senescent osteocytes not only damage their local microenvironment, but also induce “senescence-induced senescence” or bystander effects in neighboring cells [39].”
BackgroundCytokines that promote periodontal tissue destruction.
Graves, D. (2008) · The Journal of Periodontology · doi:10.1902/jop.2008.080183 · Cited by 746 · cited 1× · see citing works
“Although inflammatory cytokine production is a key intermediate mechanism between bacterial challenge and host periodontal tissue destruction [15], some gram-negative products can also act as genotoxic agents inducing a DNA damage response and mitotic arrest [16].”
BackgroundHistone H2AX phosphorylation: a marker for DNA damage.
Sharma, A., Singh, K., & Almasan, A. (2012) · Methods in molecular biology · doi:10.1007/978-1-61779-998-3_40 · Cited by 679 · cited 13× · see citing works
“Then, cells were incubated with γH2AX primary antibody (1:300), or p53 (phospho-S15) (1:100) for 1 hour, washed three times, and incubated with the secondary antibody (goat α-rabbit Alexa 447) for 1 hour at room temperature.”
BackgroundInfluentialIdentification of senescent cells in the bone microenvironment
Farr, J. N., Fraser, D. G., Wang, H., Jaehn, K., Ogrodnik, M. B., Weivoda, M. M., Drake, M. T., Tchkonia, T., LeBrasseur, N. K., Kirkland, J. L., et al. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2892 · Cited by 562 · cited 7× · see citing works
“For fluorescent in situ hybridization (FISH) staining, bone sections were processed as previously described [23].”
BackgroundMethodInfluentialSelf-citationPeriodontal Disease as a Specific, albeit Chronic, Infection: Diagnosis and Treatment
Loesche, W., & Grossman, N. (2001) · Clinical Microbiology Reviews · doi:10.1128/cmr.14.4.727-752.2001 · Cited by 543 · cited 1× · see citing works
“Periodontitis is the most common chronic bacterial infection and osteolytic disease, leading to edentulism and affecting life quality and general health [1, 2].”
BackgroundCoppé, J.-P., Rodier, F., Patil, C. K., Freund, A., Desprez, P.-Y., & Campisi, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.257071 · Cited by 506 · see citing works
Robles, S. J., & Adami, G. R. (1998) · Oncogene · doi:10.1038/sj.onc.1201862 · Cited by 498 · see citing works
The inflammophilic character of the periodontitis-associated microbiota
Hajishengallis, G. (2014) · Molecular Oral Microbiology · doi:10.1111/omi.12065 · Cited by 407 · cited 4× · see citing works
“Thus, it is the host inflammatory reaction that primarily and ultimately causes alveolar bone resorption [5].”
BackgroundInfluentialMicrobial shift and periodontitis
Berezow, A. B., & Darveau, R. P. (2010) · Periodontology 2000 · doi:10.1111/j.1600-0757.2010.00350.x · Cited by 400 · cited 1× · see citing works
“Transition from health to disease in the periodontium is associated with a gradual change from a symbiotic to a pathogenic host-microbial relationship [3, 4].”
BackgroundMatrix Metalloproteinases as Regulators of Periodontal Inflammation
Cavalla, F., Hernández‐Ríos, P., Timo, S., Claudia, B., & Hernández, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020440 · Cited by 342 · see citing works
Animal Models for Periodontal Disease
Oz, H. S., & Puleo, D. (2011) · Journal of Biomedicine and Biotechnology · doi:10.1155/2011/754857 · Cited by 323 · cited 1×
“Given that mice naturally develop periodontal disease starting around 9 months of age [41], our finding that 30% of dysfunctional senescent osteocytes are already present at 6 months appears to precede the onset of alveolar bone loss.”
BackgroundFarr, J. N., & Khosla, S. (2019) · Bone · doi:10.1016/j.bone.2019.01.015 · Cited by 263 · see citing works
Self-citationSwanson, E. C., Manning, B., Zhang, H., & Lawrence, J. B. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201306073 · Cited by 251 · cited 2× · see citing works
“A senescent osteocyte was defined based on the number of SADS per cell, with a cut-off of ≥ 4 [23, 24].”
MethodResultQUANTITATIVE GENETICS OF GEOMETRIC SHAPE IN THE MOUSE MANDIBLE
Klingenberg, C., & Leamy, L. (2001) · Evolution; international journal of organic evolution · doi:10.1554/0014-3820(2001)055[2342:qgogsi]2.0.co;2 · Cited by 237 · see citing works
Isolation and Culture of Primary Osteocytes from the Long Bones of Skeletally Mature and Aged Mice
Stern, A. R., Stern, M. M., Dyke, M. E. V., Jähn, K., Prideaux, M., & Bonewald, L. F. (2012) · BioTechniques · doi:10.2144/0000113876 · Cited by 207 · see citing works
Techniques to induce and quantify cellular senescence
Noren Hooten, N., & Evans, M. K. (2017) · Journal of Visualized Experiments · doi:10.3791/55533 · Cited by 178 · cited 1× · see citing works
“For senescence-associated β-galactosidase assay (SA-β-gal), cells were cultured in 6-well plates, and then the staining was performed following a previously described protocol [27].”
MethodPeriodontitis and systemic diseases: A literature review
Arigbede, A., Babatope, B., & Bamidele, M. (2012) · Journal of Indian Society of Periodontology · doi:10.4103/0972-124x.106878 · Cited by 164 · cited 1×
“Periodontitis is the most common chronic bacterial infection and osteolytic disease, leading to edentulism and affecting life quality and general health [1, 2].”
BackgroundCellular Senescence and the Biology of Aging, Disease, and Frailty
LeBrasseur, N. K., Tchkonia, T., & Kirkland, J. L. (2015) · Nestlé Nutrition Institute Workshop Series · doi:10.1159/000382054 · Cited by 147 · cited 1× · see citing works
“Indeed, cellular senescence and SASP factors play a crucial role in the genesis and/or progression of age-related diseases [40].”
BackgroundMatrix Metalloproteinase‐13 Is Highly Expressed in Destructive Periodontal Disease Activity
Hernández, M., Valenzuela, M. A., López-Otı́n, C., Álvarez, J., López, J. M., Vernal, R., & Gamonal, J. A. (2006) · Journal of Periodontology · doi:10.1902/jop.2006.050461 · Cited by 126 · see citing works
Guerra, L., Guidi, R., & Frisan, T. (2011) · FEBS Journal · doi:10.1111/j.1742-4658.2011.08125.x · Cited by 99 · cited 1× · see citing works
“Although inflammatory cytokine production is a key intermediate mechanism between bacterial challenge and host periodontal tissue destruction [15], some gram-negative products can also act as genotoxic agents inducing a DNA damage response and mitotic arrest [16].”
BackgroundBacterial intoxication evokes cellular senescence with persistent DNA damage and cytokine signalling
Blažková, H., Krejcikova, K., Moudrý, P., Frisan, T., Hodny, Z., & Bartek, J. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00862.x · Cited by 99 · cited 2× · see citing works
“In addition to replicative senescence, which is associated with aging phenotypes, stressinduced senescence is also observed following persistent DNA damage resulting from oncogenic or oxidative stress [6, 7].”
BackgroundFeng, X., Feng, G., Xing, J., Shen, B., Tan, W., Huang, D. Y., Lu, X., Tao, T., Zhang, J., Li, L., et al. (2014) · Cell and Tissue Research · doi:10.1007/s00441-014-1799-7 · Cited by 88 · see citing works
Graves, D., Alshabab, A., Albiero, M. L., Mattos, M., Corrêa, J., Chen, S., & Yang, Y. (2018) · Journal of Clinical Periodontology · doi:10.1111/jcpe.12851 · Cited by 77 · cited 2× · see citing works
“Recently, it was reported that osteocytes play a crucial role in bacterial-induced alveolar bone destruction by expressing RANKL [38].”
BackgroundRepeated Lipopolysaccharide Stimulation Induces Cellular Senescence in BV2 Cells
Yu, H.-M., Zhao, Y.-M., Luo, X.-G., Feng, Y., Ren, Y., Shang, H., He, Z.-Y., Luo, X.-M., Chen, S.-D., & Wang, X.-Y. (2012) · Neuroimmunomodulation · doi:10.1159/000330254 · Cited by 76 · see citing works
Kim, C., Huh, A., Han, S. H., & Kim, J. (2012) · Archives of gerontology and geriatrics (Print) · doi:10.1016/j.archger.2011.07.016 · Cited by 56 · cited 1× · see citing works
“Indeed, repeated LPS exposure, a gram-negative bacterial outer membrane component, can induce senescence in microglial [17], dental pulp [13] and pulmonary epithelial cells [18].”
BackgroundZhao, M., & Chen, X. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00601.2014 · Cited by 48 · cited 1× · see citing works
“Given that agents that cause DNA damage may lead to premature senescence [29] and repeated LPS stimulation induces premature senescence in adipocyte progenitors [30], we next examined the effects of LPS on γH2AX, a recognized marker of DNA damage [31].”
BackgroundmiR-219a-5p Regulates Rorβ During Osteoblast Differentiation and in Age-related Bone Loss
Aquino-Martinez, R., Farr, J. N., Weivoda, M. M., Negley, B. A., Onken, J. L., Thicke, B. S., Fulcer, M., Fraser, D. G., VanWijnen, A., Khosla, S., et al. (2018) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3586 · Cited by 43 · see citing works
Self-citationP53 mediates lipopolysaccharide‐induced inflammation in human gingival fibroblasts
Liu, J., Zeng, J., Wang, X., Zheng, M., & Luan, Q. (2018) · Journal of Periodontology · doi:10.1002/jper.18-0026 · Cited by 43 · cited 1× · see citing works
“In agreement with this finding, it was recently reported that LPS induces the increased secretion of Il1α, Il6 and Tnfα through p53-dependent activation in human gingival fibroblasts [42].”
BackgroundSenescence helps regeneration.
Serrano, M. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.12.007 · Cited by 36 · cited 2× · see citing works
“On the other hand, in agreement with the role of SASP factors in promoting tissue remodeling [9, 44], Mmp13 was consistently upregulated.”
BackgroundThe use of rats and mice as animal models in ex vivo bone growth and development studies
Abubakar, A. A., Noordin, M., Azmi, T., Kaka, U., & Loqman, M. (2016) · Bone & Joint Research · doi:10.1302/2046-3758.512.bjr-2016-0102.r2 · Cited by 34 · see citing works
An Ex Vivo Rodent Mandible Culture Model for Bone Repair
Smith, E. L., Locke, M., Waddington, R., & Sloan, A. (2010) · Tissue Engineering. Part C, Methods · doi:10.1089/ten.tec.2009.0698 · Cited by 34 · cited 1× · see citing works
“Indeed, the ex vivo murine mandible culture model represents an “ideal system” to substitute for in vivo studies, are ethically acceptable, and have been validated for the study of inflammatory bone destruction in the presence of LPS [34, 35].”
BackgroundA Novel Ex vivo Culture Model for Inflammatory Bone Destruction
Sloan, A., Taylor, S., Smith, E. L., Roberts, J., Chen, L., Wei, X.-Q., & Waddington, R. (2013) · Journal of dentistry research · doi:10.1177/0022034513495240 · Cited by 25 · cited 1× · see citing works
“Indeed, the ex vivo murine mandible culture model represents an “ideal system” to substitute for in vivo studies, are ethically acceptable, and have been validated for the study of inflammatory bone destruction in the presence of LPS [34, 35].”
BackgroundDo senescence markers correlate in vitro and in situ within individual human donors?
Waaijer, M., Gunn, D., van Heemst, D., Slagboom, P., Sedivy, J., Dirks, R., Tanke, H., Westendorp, R., & Maier, A. B. (2018) · Aging · doi:10.18632/aging.101389 · Cited by 21 · cited 1× · see citing works
“Given that p16Ink4a is one of the most robust and well-characterized senescent cell biomarkers along with p53 and p21 [28], we initially evaluated their expression in an osteocyte-enriched cell population from alveolar bone compared with similarly isolated cells from ramus bone, without in vitro culture.”
BackgroundCharacterization of primary osteocyte-like cells from rat mandibles
Zakhary, I. E., Wenger, K., Elsalanty, M., Cray, J., Sharawy, M. M. H., & Messer, R. (2016) · Oral surgery, oral medicine, oral pathology and oral radiology · doi:10.1016/j.oooo.2016.08.020 · Cited by 2 · see citing works
Flagged first, then by citations
4 of the 49 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- [36]Chen QM, Tu VC, Catania J, Burton M, Toussaint O, Dilley T, Involvement of Rb family proteins, focal adhesion proteins and protein synthesis in senescent morphogenesis induced by hydrogen peroxide, J Cell Sci 113 (Pt 22) (2000) 4087– 4097. 11058095
Cited by
Sorted by citations
Osteoporosis and periodontal diseases – An update on their association and mechanistic links
Yu, B., & Wang, C.-Y. (2022) · Periodontology 2000 · doi:10.1111/prd.12422 · Cited by 379 · see citing works
Periodontal Disease: The Good, The Bad, and The Unknown
Sedghi, L. M., Bacino, M. S., & Kapila, Y. L. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.766944 · Cited by 385 · see citing works
Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics
Chandra, A., & Rajawat, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073553 · Cited by 276 · see citing works
Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion
Okumura, S., Konishi, Y., Narukawa, M., Sugiura, Y., Yoshimoto, S., Arai, Y., Sato, S., Yoshida, Y., Tsuji, S., Uemura, K., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25965-x · Cited by 264 · see citing works
Frailty, aging, and periodontal disease: Basic biologic considerations
Clark, D. L., Kotronia, E., & Ramsay, S. E. (2021) · Periodontology 2000 · doi:10.1111/prd.12380 · Cited by 159 · see citing works
Oxylipin-PPARγ-initiated adipocyte senescence propagates secondary senescence in the bone marrow
Liu, X., Gu, Y., Kumar, S., Amin, S., Guo, Q., Wang, J., Fang, C.-L., Cao, X., & Wan, M. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.03.005 · Cited by 137 · see citing works
The roles of osteocytes in alveolar bone destruction in periodontitis
Huang, X., Xie, M.-R., Xie, Y.-L., Mei, F., Lu, X., Li, X.-S., & Chen, L.-L. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02664-7 · Cited by 110 · see citing works
“The accumulation of senescent osteocytes in young alveolar bone with respect to the ramus has been observed by measuring senescence-associated distension of satellites, a marker of cellular senescence, accompanied by upregulation of SASP expression [81].”
BackgroundInfluentialSenescence-associated secretory phenotype and its impact on oral immune homeostasis
Yue, Z., Nie, L., Zhao, P., Ji, N., Liao, G., & Wang, Q. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1019313 · Cited by 94 · see citing works
Li, Y., Huang, Z., Pan, S.-S., Feng, Y., He, H., Cheng, S.-G., Wang, L., Wang, L., & Pathak, J. (2023) · Nutrients · doi:10.3390/nu15092115 · Cited by 87 · see citing works
Aquino‐Martinez, R., Eckhardt, B. A., Rowsey, J. L., Fraser, D. G., Khosla, S., Farr, J. N., & Monroe, D. G. (2021) · Journal of Periodontology · doi:10.1002/jper.20-0529 · Cited by 78 · see citing works
Self-citationThe Role of Neutrophil Extracellular Traps in Periodontitis
Wang, J., Zhou, Y., Ren, B., Zou, L., He, B., & Li, M. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.639144 · Cited by 75 · see citing works
Elsayed, R., Elashiry, M., Liu, Y., El-Awady, A., Hamrick, M., & Cutler, C. W. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.669989 · Cited by 64 · see citing works
Sadek, K. M., Moshy, S. E., Radwan, I. A., Rady, D., Abbass, M. M. S., El‐Rashidy, A. A., Dörfer, C. E., & El‐Sayed, K. M. F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054599 · Cited by 62 · see citing works
Cellular Senescence and Periodontitis: Mechanisms and Therapeutics
Chen, S., Zhou, D., Liu, O., Chen, H., Wang, Y., & Zhou, Y. (2022) · Biology · doi:10.3390/biology11101419 · Cited by 49 · see citing works
“The bacterial-derived LPS not only plays a role in the obtaining of “premature” cellular senescence, but also may promote the secretion of the SASP that aggravates localized inflammation, eventually leading to alveolar bone loss [68].”
BackgroundInfluentialSevere COVID-19 Lung Infection in Older People and Periodontitis
Aquino-Martínez, R., & Vigueras, S. H. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10020279 · Cited by 76 · see citing works
“Of note, IL-17 plays an important role in periodontal disease pathogenesis, and it is secreted by senescent alveolar bone osteocytes [125,156].”
BackgroundSelf-citationPeriodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem?
Aquino-Martínez, R., Khosla, S., Farr, J. N., & Monroe, D. G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207441 · Cited by 54 · see citing works
“Recently, our group identified the presence of i creased DNA damage and abnormal accumul tion of senescent cells in young periodontal tissues usi g a murine model [13].”
BackgroundResultInfluentialSelf-citationLipopolysaccharides and Cellular Senescence: Involvement in Atherosclerosis
Suzuki, K., Susaki, E. A., & Nagaoka, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911148 · Cited by 54 · see citing works
“gingivalis 10 ng/mL, 6 days Mouse periodontal alveolar osteocytes + ICAM-1, IL-1β, IL-6, IL-8, MCP1, MMP12, MMP13 p16, p21, p53 Disordered distribution of F-actin [84]”
BackgroundAssessment of Changes in the Oral Microbiome That Occur in Dogs with Periodontal Disease
Santibáñez, R., Rodríguez-Salas, C., Flores-Yáñez, C., Garrido, D., & Thomson, P. (2021) · Veterinary Sciences · doi:10.3390/vetsci8120291 · Cited by 49
Inflammatory and Immunological Basis of Periodontal Diseases
Baima, G., Arce, M., Romandini, M., & Dyke, T. E. V. (2025) · Journal of Periodontal Research · doi:10.1111/jre.70040 · Cited by 49 · see citing works
Akkaoui, J., Yamada, C., Duarte, C. L., Ho, A., Vardar‐Şengül, S., Kawai, T., & Movilă, A. (2020) · GeroScience · doi:10.1007/s11357-020-00258-1 · Cited by 53 · see citing works
Senescent cells: A therapeutic target for osteoporosis
Wang, T., Huang, S., & He, C. (2022) · Cell Proliferation · doi:10.1111/cpr.13323 · Cited by 43 · see citing works
“LPS exposure also enhances the production of proinflammatory factors, including intercellular cell adhesion molecule-1 (ICAM1), IL-6, monocyte chemoattractant protein-1 (MCP1), MMP12 and MMP13.(209) In an”
BackgroundInfluentialAging and Mesenchymal Stem Cells: Therapeutic Opportunities and Challenges in the Older Group
Chen, H., Liu, O., Chen, S., & Zhou, Y. (2021) · Gerontology · doi:10.1159/000516668 · Cited by 51 · see citing works
Qin, Z., Gu, X., Chen, Y., Liu, J., Hou, C.-X., Lin, S., Hao, N., Liang, Y., Chen, W., & Meng, H. (2020) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2020.4787 · Cited by 46 · see citing works
González, L., Sierra‐Cristancho, A., Cafferata, E. A., Melgar-Rodríguez, S. A., Rojas, C., Carvajal, P., Cortéz, C., & Vernal, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052543 · Cited by 43 · see citing works
Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration
Herrmann, M., Diederichs, S., Melnik, S., Riegger, J., Trivanović, D. I., Li, S., Jenei‐Lanzl, Z., Brenner, R. E., Huber-Lang, M. S., Zaucke, F., et al. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.624096 · Cited by 41 · see citing works
“RNA-sequencing and liquid chromatography-mass (LCM) spectrometry analysis revealed that several SASP proteins, including TGF-β2, osteoprotegrin (OPG), MMP-9, TIMP1, macrophage migration inhibitory factor (MIF)-1, peroxiredoxins (PRDXs), and insulin-like growth factor binding protein (IGFBP) 3, were upregulated in EVs…”
MethodThe Emerging Role of Accelerated Cellular Senescence in Periodontitis
Aquino-Martinez, R. (2023) · Journal of dentistry research · doi:10.1177/00220345231154567 · Cited by 39 · see citing works
“On the other hand, Porphyromonas gingivalis lipopolysaccharide (LPS) repeated exposure causes a “senescent-like” phenotype in alveolar bone cells by causing DNA damage (Aquino-Martinez et al. 2020, 2021).”
BackgroundInfluentialSelf-citationRecent advances in senescence-associated secretory phenotype and osteoporosis
Fan, H., Qiao, Z., Li, J., Shang, G., Shang, C., Chen, S., Leng, Z., Su, H., Kou, H., & Liu, H. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e25538 · Cited by 42 · see citing works
“Furthermore, LPS promotes the development of premature osteocyte senescence and the secretion of proinflammatory factors, triggering inflammatory bone loss [108].”
BackgroundDing, Z., Ma, G., Zhou, B., Cheng, S., Tang, W., Han, Y., Chen, L., Pang, W., Chen, Y., Yang, D., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101665 · Cited by 31 · see citing works
The impact of ageing mechanisms on musculoskeletal system diseases in the elderly
Cai, Y., Han, Z., Cheng, H., Li, H., Wang, K., Chen, J., Liu, Z., Xie, Y., Lin, Y., Zhou, S., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1405621 · Cited by 47 · see citing works
Periodontal disease as a model to study chronic inflammation in aging
Bertolini, M., & Clark, D. R. (2023) · GeroScience · doi:10.1007/s11357-023-00835-0 · Cited by 37 · see citing works
“Senescent cells have been identified via the expression of the marker p16Ink4a within the bone that supports the dentition [105].”
Yamada, C., Ho, A., Akkaoui, J., Garcia, C., Duarte, C., & Movila, A. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111503 · Cited by 33 · see citing works
“A triterpenoid saponin glycoside glycyrrhizin (GLY), an active component of licorice plant roots (Glycyrrhiza glabra), possesses multiple pharmacological properties, including anti-inflammation, anti-tumor, anti-aging, and anti-oxidative activities [21–23] It was also suggested that GLY attenuates tissue aging and pro…”
BackgroundYamada, C., Akkaoui, J., Ho, A., Duarte, C. L., Deth, R. C., Kawai, T., Nichols, F. C., Lakshmana, M. K., & Movilă, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.591571 · Cited by 31 · see citing works
“gingvalis induces premature cellular senescence (48) as well as promotes”
BackgroundSystemic, Lifestyle and Environmental Modifying Factors in the Pathogenesis of Periodontitis
Groeger, S. E., Yuxi, Z., Yong, J., Wang, L., Ruf, S., & Meyle, J. (2025) · Journal of Periodontal Research · doi:10.1111/jre.70003 · Cited by 25 · see citing works
Rejuvenation of Mesenchymal Stem Cells to Ameliorate Skeletal Aging
Cheng, M., Yuan, W., Moshaverinia, A., & Yu, B. (2023) · Cells · doi:10.3390/cells12070998 · Cited by 33 · see citing works
“In the context of periodontitis, aging, hyperglycemia and bacterial lipopolysaccharide (LPS) induce cellular senescence in gingival fibroblasts and macrophages to aggravate the adaptive immune response and periodontal inflammation [2,7,22].”
BackgroundVerbruggen, S. W., Nolan, J., Duffy, M. P., Pearce, O. M. T., Jacobs, C., & Knight, M. M. (2023) · Advancement of science · doi:10.1002/advs.202305842 · Cited by 29 · see citing works
Does Periodontitis Affect the Association of Biological Aging with Mortality?
Liu, Y., Xu, S., Cai, Q., Chen, Y., Zhu, P., Du, M., Visser, A., & Li, A. (2023) · Journal of dentistry research · doi:10.1177/00220345231179117 · Cited by 26
“A study showed that after alveolar osteocytes were treated with bacteria-derived lipopolysaccharide (LPS), the expression of various senescence and SASP markers and the hallmarks of cellular senescence increased (Aquino-Martinez et al. 2020).”
BackgroundAnalysis of senescence in gingival tissues and gingival fibroblast cultures
Furukawa, M., Matsuda, K., Aoki, Y., Yamada, M., Wang, J., WATANABE, M., Kurosawa, M., Shikama, Y., & Matsushita, K. (2022) · Clinical and Experimental Dental Research · doi:10.1002/cre2.581 · Cited by 23 · see citing works
The Role of Senescence-Associated Secretory Phenotype in Bone Loss
Zhu, R., Wan, H., Yang, H. S., Song, M., Chai, Y., & Yu, B. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.841612 · Cited by 21 · see citing works
Souza, N. C., Nascimento, E. N. D. O., de Oliveira, I. B., Oliveira, H. M. L., Santos, E. G., Mata, M. E. R. M. C., Gelain, D., Moreira, J., Dalmolin, R., & Pasquali, M. A. D. B. (2020) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2020.110277 · Cited by 20
Amato, M., Polizzi, A., Viglianisi, G., Leonforte, F., Mascitti, M., & Isola, G. (2025) · Metabolites · doi:10.3390/metabo15010035 · Cited by 21 · see citing works
Roato, I., Baima, G., Orrico, C., Balma, A. M., Alotto, D., Romano, F., Ferracini, R., Aimetti, M., & Mussano, F. (2023) · Biomedicines · doi:10.3390/biomedicines11092535 · Cited by 19 · see citing works
Lipopolysaccharide-Induced Immunological Tolerance in Monocyte-Derived Dendritic Cells
Mbongue, J. C., Vanterpool, E., Firek, A. F., & Langridge, W. H. R. (2022) · Immuno · doi:10.3390/immuno2030030 · Cited by 23 · see citing works
Molecular profiling of intrabony defects' gingival crevicular fluid.
Koidou, V. P., Hagi-Pavli, E., Cross, S., Nibali, L., & Donos, N. (2021) · Journal of Periodontal Research · doi:10.1111/jre.12948 · Cited by 19
Fu, L.-L., Yin, C., Zhao, Q., Guo, S., Shao, W.-J., Xia, T., Sun, Q., Chen, L., Li, J.-H., Wang, M., et al. (2025) · bioRxiv · doi:10.1101/2024.02.21.581332 · Cited by 18 · see citing works
“Recent studies have also found that repeated exposure to LPS, a component of gram-negative bacterial membranes, leads to DNA damage in various cell types, including gingival and alveolar bone cells ( Aquino-Martinez et al., 2020 ).”
Huang, Y.-K., Wang, D.-Q., Zhang, W., Yuan, X., Li, K., Zhang, Y., & Zeng, M.-Q. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.18043 · Cited by 17 · see citing works
Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis
Kumar, S., Song, K., Wang, J., Baghel, M. S., Zeng, Y., Shen, K., Zheng, J., Crane, J., Demehri, S., Gao, P., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00924-z · Cited by 16 · see citing works
“Immunofluorescence using the DNA damage marker γH2AX, a robust marker of senescent cells 50–52 , also revealed a substantial increase in γH2AX + BMAds in both AD mice (Fig.”
Pexidartinib Inhibits Macrophage Senescence Through Glycolysis in Periodontitis Microenvironment
Zhan, J., Kang, J., Wei, Y., Xiao, T.-J., Fang, H., Li, L., Yuan, Y., Zhang, Y.-C., Zhang, J., & Tian, A. (2025) · International Dental Journal · doi:10.1016/j.identj.2025.100843 · Cited by 16 · see citing works
Dasatinib and Quercetin Mitigate Age‐Related Alveolar Bone Inflammaging and Neutrophil Infiltration
Tang, J., Li, J., Hou, Z., He, R., Li, B., Gong, J., Xie, Y., Meng, W., Liu, Y., Ouchi, T., et al. (2025) · Oral Diseases · doi:10.1111/odi.15291 · Cited by 16 · see citing works
Immunosenescence and inflammaging: Conspiracies against alveolar bone turnover
Zhou, F., Wang, Z., Zhang, G., Wu, Y., & Xiong, Y. (2023) · Oral Diseases · doi:10.1111/odi.14642 · Cited by 16 · see citing works
Zhong, Y., Zhang, Y., Liu, W.-F., Zhao, Y., Zou, L., & Liu, X.-X. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/7202837 · Cited by 13 · see citing works
“TLR4-activated alveolar bone osteocytes showed upregulated mRNA expression of p16, p21, and p53, overexpressed SASP factors, and severe DNA damage [25].”
BackgroundRetractedPhotoacoustic Imaging for Periodontal Disease Examination.
Sari, A. W., Widyaningrum, R., & Yana, M. (2021) · Journal of lasers in medical sciences · doi:10.20944/preprints202107.0529.v1 · Cited by 12
Cellular senescence: A new perspective on the suppression of periodontitis (Review)
Lin, X.-J., Yuan, Q., Zhou, J., Dong, Y., Sunchuri, D., & Guo, Z.-L. (2024) · Molecular Medicine Reports · doi:10.3892/mmr.2024.13362 · Cited by 12 · see citing works
“…β ‑galactosidase, increase the expression levels of cell cycle inhibitor proteins p21 and p53, and impede human pulp stem cell growth (25,27,28). increased expression of lPS by P. gingivalis may stimulate nF‑ κ B activation in periodontal ligament stem cells (PdlScs), exacerbate the…”
BackgroundInvolvement of the endocannabinoid system in current and recurrent periodontitis: A human study.
Pellegrini, G., Carmagnola, D., Toma, M., Rasperini, G., Orioli, M., & Dellavia, C. (2023) · Journal of Periodontal Research · doi:10.1111/jre.13103 · Cited by 11 · see citing works
Danish, M., Diwan, B., Kumar, A., Khan, M., Awasthi, A., Sharma, L., & Sharma, R. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-10232-9 · Cited by 10 · see citing works
Nitzsche, Á., Hennig, C., von Brandenstein, K., Döding, A., Schulze‐Späte, U., Symmank, J., & Jacobs, C. (2024) · Cells · doi:10.3390/cells13020147 · Cited by 9 · see citing works
“OTM can be interfered by a number of pharmaceuticals, which may also induce functional disturbances that affect bone resorption or attachment processes [26,27].”
BackgroundThe Role of Cellular Senescence in Oral Health and Disease
Elashiry, M., Timothius, C. J. C., Zaman, R., Elliott, M., Crosby, B., Bhat, K., Saad, K. M., & Elsayed, R. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27052269 · Cited by 9
“With aging, cumulative stressors reduce osteogenic potential and increase susceptibility to bone resorption [62,107,108,127,128].”
InfluentialOsteocyte dysregulation in periodontitis: Pathological mechanisms and therapeutic potential
Si, L., Tian, X., Tian, L., & Yang, K. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.112062 · Cited by 8 · see citing works
SIRT6 alleviates senescence induced by Porphyromonas gingivalis in human gingival fibroblasts
Shi, J., Hao, X., Tong, Y., Qian, W.-B., & Sun, Y. (2024) · Molecular Biology Reports · doi:10.1007/s11033-024-09913-8 · Cited by 9 · see citing works
“Ruben revealed that continuous P. gingivalis LPS stimulation induced osteoblast senescence, leading to excessive secre - tion of SASP factors and further accumulation of senescent osteoblasts in the alveolar bone of young mice [ 34 ].”
Bae, W.-J., & Lee, S.-I. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104959 · Cited by 8 · see citing works
Characterization of senescence and nuclear reorganization in aging gingival cells
Fernández, C., Ormeño, D., Villalobos, V., Garrido, M., Canelo, J., Cerda, O., Maldonado, F., & Cáceres, M. (2025) · npj Aging · doi:10.1038/s41514-025-00200-9 · Cited by 8 · see citing works
Zhao, J., Jiao, J., Chen, X., Zhang, Y., Chen, T., Xie, J.-H., & Ou, X.-Y. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113435 · Cited by 8 · see citing works
SIRT7 inhibits the aging and inflammatory damage of hPDLFs by suppressing the AKT/mTOR.
Sun, J., Li, Y., Meng, M.-H., Zeng, X., Wang, Q., Li, W.-J., Luo, Y., Chen, H.-P., & Dong, Q. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113300 · Cited by 8 · see citing works
Zhou, C.-C., Xu, R.-S., Wu, Z., Zhang, Z.-W., Yuan, Q., Zou, S.-J., Xie, J., & Zhang, D.-M. (2021) · The Chinese journal of dental research : the official journal of the Scientific Section of the Chinese Stomatological Association · doi:10.3290/j.cjdr.b1105871 · Cited by 8
Kim, S. J., Batra, C., Yoshii, H., Hamada, Y., Ueki, Y., Eckert, G. J., John, V., & Kittaka, M. (2025) · The Journal of Periodontology · doi:10.1002/jper.11393 · Cited by 7 · see citing works
Kang, J., Zhan, J., Yuan, Y., Wei, Y., Xiao, T.-J., Li, L., Fang, H., & Tian, A. (2025) · Scientific Reports · doi:10.1038/s41598-025-13153-6 · Cited by 7 · see citing works
Ma, P.-C., Wang, R., Chen, H.-Z., Zheng, J.-C., Yang, W., Meng, B., Liu, Y.-F., Lu, Y., Zhao, J., & Gao, H.-W. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1535666 · Cited by 7
Shenker, B. J., Korostoff, J. M., Walker, L. M., Zekavat, A., Dhingra, A., Kim, T. J., & Boesze‐Battaglia, K. (2024) · Pathogens · doi:10.3390/pathogens13020155 · Cited by 6 · see citing works
“While direct evidence of a role for senescence in periodontal disease is currently limited, there is increasing acknowledgment of its potential participation in age-associated alterations within the periodontal environment as it relates to disease susceptibility [51,76,77].”
BackgroundAlexakou, E., Bakopoulou, A., Apatzidou, D., Kritis, A., Malousi, A., & Anastassiadou, V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010005 · Cited by 7 · see citing works
“G1a received no treatment (negative control group).”
Photosensitizers attenuate LPS-induced inflammation: implications in dentistry and general health
Couto, A., de Carvalho, R. D., Brancini, G. T. P., Martins, F., Sorgi, C., da Silva, R. A. B., Nelson-Filho, P., Paula-Silva, F. W., Borsatto, M. C., Braga, G. U., et al. (2020) · Lasers in Medical Science · doi:10.1007/s10103-020-03180-2 · Cited by 7
Neutrophils at the Crossroads of Oral Microbiome Dysbiosis and Periodontal Disease
Viana, J., Ferro, T., Pitschieller, R., Machado, V., Su, N., Mendes, J. J., & Botelho, J. (2025) · Microorganisms · doi:10.3390/microorganisms13112573 · Cited by 6 · see citing works
“Potential therapeutic approaches for periodontitis include regulating NET concentrations, local anti-inflammatory therapy, and targeted antibacterial treatments [32].”
PKM2+ apoptotic vesicle-mediated systemic senolytics ameliorate chronic periodontitis
Hao, M., Yan, X., Jiang, Y.-X., Li, W.-W., Cao, Z.-Y., Zhang, M.-J., Li, P., Li, C., & Shi, S. (2025) · Bioactive Materials · doi:10.1016/j.bioactmat.2025.06.041 · Cited by 6 · see citing works
“The accumulation of senescent cells in diseased regions is a common occurrence in localized inflammatory conditions, including periodontitis, arthritis, and pneumonia [56 – 59].”
Wei, Y., & Peng, Z. (2022) · Annals of Translational Medicine · doi:10.21037/atm-22-4209 · Cited by 6 · see citing works
“Research has shown that LPS participates in the destruction of periodontal tissues (29).”
Xu, Y.-X., Zheng, J., Liu, M., Fu, Z.-H., & Wang, P. (2025) · Stem Cells International · doi:10.1155/sci/7639451 · Cited by 5 · see citing works
Teawcharoensopa, C., & Srisuwan, T. (2023) · Clinical Oral Investigations · doi:10.1007/s00784-023-05455-8 · Cited by 5 · see citing works
“For instance, previous studies using repeated stimulation of 10 ng/ml E.coli LPS for 36 h and P. gingivalis for 144 h reported cellular senescence induction in dental pulp stem cells [28] and alveolar osteocytes [29], respectively.”
Cheng, J., Aung, C. T. Z., Suslavich, S. F., Sahingur, S. E., & Kapila, Y. L. (2026) · Periodontology 2000 · doi:10.1111/prd.70049 · Cited by 2 · see citing works
Zhang, X., Li, L.-S., Liu, H.-R., Zhang, Y.-G., Wu, Y., Sun, C., Guo, J., & Li, M.-Q. (2026) · Cellular Signalling · doi:10.1016/j.cellsig.2026.112442 · Cited by 4 · see citing works
Zhang, Y., Chu, J., Yu, Z., & Gong, Y. (2025) · Placenta · doi:10.1016/j.placenta.2025.06.009 · Cited by 4 · see citing works
The Tripartite Nexus Among Oral Microbiome, DNA Repair, and Aging
Wang, K., Li, J., Tang, Y., Mao, Z.-Y., & Chen, Y. (2025) · Oral Science and Homeostatic Medicine · doi:10.26599/oshm.2025.9610004 · Cited by 4
Lee, S., Kim, J.-H., Kim, M., Hong, S., Park, H., Kim, E. J., Kim, E.-Y., Lee, C.-H., Sohn, Y., & Jung, H.-S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216465 · Cited by 4 · see citing works
Osteoimmune senescence in aging-related bone diseases
Li, H., Yang, Y., & Zhu, H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1892334 · Cited by 5 · see citing works
Dasatinib and quercetin prevent alveolar bone loss in aged mice
Battistelli, L. S., Moraes, R. M., Santos, Y. C., Ribeiro, J. L., Garcia, M. T., do Prado, R. F., Elefteriou, F., & Anbinder, A. L. (2026) · Journal of Periodontology · doi:10.1002/jper.70115 · Cited by 3 · see citing works
Ibarra-Sánchez, A., Madera-Salcedo, I., Esparza‐Reyes, D., Mendoza‐Montiel, P., Padilla, J., & González-Espinosa, C. (2025) · Aging Cell · doi:10.1111/acel.70186 · Cited by 3 · see citing works
“Prolonged exposure to LPS promotes the expression of senescence markers in distinct cell types (Aquino-Martinez et al. 2020; Kim et al. 2012), including macrophages (Fang et al. 2024; Danish et al. 2025).”
Kou, Y.-N., Guo, W.-Y., Wang, Y., Kou, C., & Zhang, B. (2024) · Photochemistry and Photobiology · doi:10.1111/php.14039 · Cited by 3
“36 The expression of β - galactosidase was modest in young cells, while the enzyme was highly expressed in older cells.”
Gupta, S., Mohindra, R., Ramola, M., Kanta, P., Singla, M., Malhotra, M., Mehta, N., Goyal, A., & Singh, M. P. (2024) · Journal of Indian Society of Periodontology · doi:10.4103/jisp.jisp_508_23 · Cited by 2 · see citing works
“[22] COVID-19 and periodontitis also share the common features of enhancing senescence and cytokine production through triggering nuclear factor kappa B pathway and p38 mitogen-activated protein kinase activation by downregulation of angiotensin-converting enzyme 2.”
LI, J., Sanui, T., Shida, M., Yotsumoto, K., Ahmad, M., Wang, Z., Xiao, M., Hayashi, C., Shinjo, T., Taketomi, T., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1806138 · Cited by 2 · see citing works
Bi, J., Chai, Y., Wang, H., Zeng, J., Liu, X., Yao, M., Liu, Y., & Xu, S. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04047-4 · Cited by 2 · see citing works
“Based on the minimum concentration recommended in the literature for LPS-induced cellular senescence models in vitro [8], as well as our prior experimental findings, a concentration of 10 µg/mL LPS was administered to simulate cellular senescence (refer to Supplementary Figure S1).”
Reddy, S. S. P., Francis, D., Logaranjani, A., Agnihotry, A., Pradhan, S., & Anil, S. (2025) · Periodontal and Implant Research · doi:10.1007/s41894-025-00152-z · Cited by 2 · see citing works
“Furthermore, chronic inflammation fosters telo - mere attrition and may serve as a secondary pathogenic mechanism through DDR activation and senescence initiation [29].”
Potencial Rol de la Periodontitis en la Severidad de COVID-19. Revisión
Hernández-Vigueras, S., & Aquino-Martinez, R. (2021) · International journal of odontostomatology · doi:10.4067/s0718-381x2021000200335 · Cited by 2 · see citing works
“El rol de la senescencia celular en periodontitis y en COVID-19 también ha sido abordado (Nehme et al., 2020; Aquino-Martinez et al., 2020a; Khosla et al., 2020).”
BackgroundInfluentialSelf-citationSkeletal Aging and Osteoporosis: Cellular Senescence and BeyondPreprint
Chandra, A., & Rajawat, J. (2021) · Preprints.org · doi:10.20944/preprints202102.0127.v1 · Cited by 2 · see citing works
Khan, I. M., Khan, S. U., Nassar, N., Khan, S., Shafiq, M., Saadeldin, I. M., Swelum, A. A., Cheng, M., & Wang, Z. (2026) · npj Biofilms and Microbiomes · doi:10.1038/s41522-026-00999-5 · Cited by 1 · see citing works
“It also exertsadetrimentaleffectonthemaintenanceofbonehomeostasis 89 .”
Chojnacka, K., & Mikulewicz, M. (2026) · MedComm – Biomaterials and Applications · doi:10.1002/mba2.70047 · Cited by 1 · see citing works
Zhang, L., Luo, D., & Bai, L. (2025) · Molecular Oral Microbiology · doi:10.1111/omi.70012 · Cited by 1 · see citing works
Zhang, H., Lin, J.-H., Chen, X., Dai, J., & Lin, H. (2024) · Endocrine journal · doi:10.1507/endocrj.ej23-0484 · Cited by 1 · see citing works
“Additionally, osteocytes are also RANKL-producing cells [34], and LPS also causes bone loss by affecting the state of osteocytes [35].”
Wu, Y., Li, B., & Yang, Z. (2026) · Odontology · doi:10.1007/s10266-026-01586-y
Yang, H.-C., Fu, E., Chin, Y.-T., Shieh, J.-S., Lin, W.-N., & Chiang, C.-Y. (2026) · Journal of Dental Sciences · doi:10.1016/j.jds.2025.07.3580
“27 In the context of periodontitis, inflammaging, a chronic, sterile, low-grade inflammatory state associated with aging, has also been proposed as a contributing factor.”
Zhuang, Y., Zhang, Y.-Z., & Xu, W.-H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1891787
“Emerging evidence highlights extracellular vesicles, particularly exosomes derived from M1-polarized macrophages, as novel mediators of intercellular communication in this context (38).”
Zambrano, M. A., Ojeda, C. H., Oritz, K. O., Hernandez, R. D., Machado, C. S., & Tamayo, A. (2026) · Journal of Clinical Immunology & Microbiology · doi:10.46889/jcim.2026.7209
“Experimental work has shown that bacterial lipopolysaccharide can induce premature osteocyte senescence, providing a mechanistic link between the microbial challenge and the aging phenotype within alveolar bone itself [2].”
Gaonkar, S., Gujar, A. N., Hemanth, M., R., K. B., Manju Prasad, M., & Krishna, N. (2026) · Genetics and Molecular Research · doi:10.4238/wsm67e83
Chen, Z.-H., Tang, Q., Tang, R., Yang, Y.-M., Cai, W., Guo, R., Shao, J., & Fang, F.-C. (2026) · International Dental Journal · doi:10.1016/j.identj.2026.109720
- Authors
- Aquino-Martinez, R., Rowsey, J. L., Fraser, D. G., Eckhardt, B. A., Khosla, S., Farr, J. N., & Monroe, D. G.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Farr, Joshua N.
- Monroe, David G.
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 132
- Pages
- 115220
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- PMC
- PMC6990876
- OpenAlex
- W2997155069
- Cited by
- 114
- References
- 49
- Citations by year
- 2026: 15 · 2025: 24 · 2024: 19 · 2023: 17 · 2022: 12 · 2021: 17 · 2020: 10
- FWCI
- 8.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Bone (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Jewish National Fund (R01 AG048792)
- National Institutes of Health (P01 AG004875, R01 AR068275)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- cellular senescence, senescence-associated secretory phenotype, lipopolysaccharide, alveolar bone loss, periodontal disease, p16INK4a, γH2AX, bone resorption, inflammation, extracellular matrix remodeling, actin cytoskeleton
- MeSH terms
- Aged, Humans, Lipopolysaccharides, Osteocytes, Alveolar Bone Loss, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
