DNA damage drives accelerated bone aging via an NF- κ B–dependent mechanism
Open accessAbstract
Advanced age is one of the most important risk factors for osteoporosis. Accumulation of oxidative DNA damage has been proposed to contribute to age-related deregulation of osteoblastic and osteoclastic cells. Excision repair cross complementary group 1–xeroderma pigmentosum group F (ERCC1-XPF) is an evolutionarily conserved structure-specific endonuclease that is required for multiple DNA repair pathways. Inherited mutations affecting expression of ERCC1-XPF cause a severe progeroid syndrome in humans, including early onset of osteopenia and osteoporosis, or anomalies in skeletal development. Herein, we used progeroid ERCC1-XPF–deficient mice, including Ercc1-null (Ercc1−/−) and hypomorphic (Ercc1−/Δ) mice, to investigate the mechanism by which DNA damage leads to accelerated bone aging. Compared to their wild-type littermates, both Ercc1−/− and Ercc1−/Δ mice display severe, progressive osteoporosis caused by reduced bone formation and enhanced osteoclastogenesis. ERCC1 deficiency leads to atrophy of osteoblastic progenitors in the bone marrow stromal cell (BMSC) population. There is increased cellular senescence of BMSCs and osteoblastic cells, as characterized by reduced proliferation, accumulation of DNA damage, and a senescence-associated secretory phenotype (SASP). This leads to enhanced secretion of inflammatory cytokines known to drive osteoclastogenesis, such as interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and receptor activator of NF-κB ligand (RANKL), and thereby induces an inflammatory bone microenvironment favoring osteoclastogenesis. Furthermore, we found that the transcription factor NF-κB is activated in osteoblastic and osteoclastic cells of the Ercc1 mutant mice. Importantly, we demonstrated that haploinsufficiency of the p65 NF-κB subunit partially rescued the osteoporosis phenotype of Ercc1−/Δ mice. Finally, pharmacological inhibition of the NF-κB signaling via an I-κB kinase (IKK) inhibitor reversed cellular senescence and SASP in Ercc1−/Δ BMSCs. These results demonstrate that DNA damage drives osteoporosis through an NF-κB–dependent mechanism. Therefore, the NF-κB pathway represents a novel therapeutic target to treat aging-related bone disease. © 2013 American Society for Bone and Mineral Research.
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NF-κB activation has been observed in numerous diseases associated with aging, including sarcopenia, osteoporosis, and neurodegenerative diseases.
“NF-κB activation has been observed in numerous diseases associated with aging (91), including sarcopenia (92), osteoporosis (93), and neurodegenerative diseases (94).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [93]
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Cites
THE NF-κB AND IκB PROTEINS: New Discoveries and Insights
Baldwin, A. S. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.649 · Cited by 5,882 · see citing works
The 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 · see citing works
Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M.-S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80209-3 · Cited by 5,130 · see citing works
Neer, R. M., Arnaud, C. D., Zanchetta, J. R., Prince, R., Gaich, G. A., Reginster, J.-Y., Hodsman, A. B., Eriksen, E. F., Ish-Shalom, S., Genant, H. K., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200105103441904 · Cited by 4,602 · see citing works
Osteoporosis: now and the future
Rachner, T. D., Khosla, S., & Hofbauer, L. C. (2011) · The Lancet · doi:10.1016/s0140-6736(10)62349-5 · Cited by 2,696 · see citing works
ATM and related protein kinases: safeguarding genome integrity
Shiloh, Y. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1011 · Cited by 2,577 · see citing works
Hoeijmakers, J. H. J. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804615 · Cited by 2,239 · see citing works
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232 · see citing works
Structure, Regulation and Function of NF-kappaB
Siebenlist, U. K., Franzoso, G., & Brown, K. D. (1994) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.10.110194.002201 · Cited by 2,086 · see citing works
The TNF receptor 1-associated protein TRADD signals cell death and NF-κB activation
Hsu, H., Xiong, J., & Goeddel, D. V. (1995) · Cell · doi:10.1016/0092-8674(95)90070-5 · Cited by 2,024 · see citing works
Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB
Beg, A. A., Sha, W. C., Bronson, R. T., Ghosh, S., & Baltimore, D. (1995) · Nature · doi:10.1038/376167a0 · Cited by 1,828 · see citing works
DNA damage response and cellular senescence in tissues of aging mice
Wang, C., Jurk, D., Maddick, M., Nelson, G., Martin‐Ruiz, C., & Von Zglinicki, T. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00481.x · Cited by 696 · see citing works
A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis
Niedernhofer, L. J., Garinis, G. A., Raams, A., Lalai, A. S., Robinson, A. R., Appeldoorn, E., Odijk, H., Oostendorp, R., Ahmad, A., van Leeuwen, W., et al. (2006) · Nature · doi:10.1038/nature05456 · Cited by 669 · see citing works
Self-citationHilton, M. J., Tu, X., Wu, X., Bai, S., Zhao, H., Kobayashi, T., Kronenberg, H. M., Teitelbaum, S. L., Ross, F. P., Kopan, R., et al. (2008) · Nature Medicine · doi:10.1038/nm1716 · Cited by 604 · see citing works
Regulation of tissue homeostasis by NF-κB signalling: implications for inflammatory diseases
Pasparakis, M. (2009) · Nature reviews. Immunology · doi:10.1038/nri2655 · Cited by 523 · see citing works
NF-κB Activation: The IκB Kinase Revealed?
Stancovski, I., & Baltimore, D. (1997) · Cell · doi:10.1016/s0092-8674(00)80413-4 · Cited by 494 · see citing works
Niedernhofer, L. J., Odijk, H., Budzowska, M., van Drunen, E., Maas, A., Theil, A. F., de Wit, J., Jaspers, N. G. J., Beverloo, H. B., Hoeijmakers, J. H. J., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.13.5776-5787.2004 · Cited by 493 · see citing works
Self-citationInhibition of osteoblastic bone formation by nuclear factor-κB
Chang, J., Wang, Z., Tang, E., Fan, Z., McCauley, L. K., Franceschi, R. T., Guan, K., Krebsbach, P. H., & Wang, C.-Y. (2009) · Nature Medicine · doi:10.1038/nm.1954 · Cited by 485 · see citing works
Acharyya, S., Villalta, S. A., Bakkar, N., Bupha‐Intr, T., Janssen, P. M. L., Carathers, M., Li, Z.-W., Beg, A. A., Ghosh, S., Sahenk, Z., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30556 · Cited by 436 · see citing works
The Osteoclast: Friend or Foe?
Novack, D. V., & Teitelbaum, S. L. (2007) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.151431 · Cited by 393 · see citing works
Transcriptional Control of Skeletogenesis
Karsenty, G. (2008) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.9.081307.164437 · Cited by 390 · see citing works
Weeda, G., Donker, I., de Wit, J., Morreau, H., Janssens, R. C., Vissers, C. J., Nigg, A. L., STEEG, H. V., Bootsma, D., & Hoeijmakers, J. H. J. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00190-4 · Cited by 380 · see citing works
Telomeres: Cancer to Human Aging
Stewart, S. A., & Weinberg, R. A. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.22.010305.104518 · Cited by 336 · see citing works
McWhir, J., Selfridge, J., Harrison, D. J., Squires, S., & Melton, D. W. (1993) · Nature Genetics · doi:10.1038/ng1193-217 · Cited by 321 · see citing works
ERCC1-XPF Endonuclease Facilitates DNA Double-Strand Break Repair
Ahmad, A., Robinson, A. R., Duensing, A. U., van Drunen, E., Beverloo, H. B., Weisberg, D. B., Hasty, P., Hoeijmakers, J. H. J., & Niedernhofer, L. J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00293-08 · Cited by 298 · see citing works
Self-citationMultiple roles of ATM in monitoring and maintaining DNA integrity
Derheimer, F. A., & Kastan, M. B. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.05.031 · Cited by 256 · see citing works
Nuclear initiated NF-κB signaling: nemo and ATM take center stage
Miyamoto, S. (2011) · Cell Research · doi:10.1038/cr.2010.179 · Cited by 253 · see citing works
Ruocco, M. G., Maeda, S., Park, J. M., Lawrence, T., Hsu, L.-C., Cao, Y., Schett, G., Wagner, E. F., & Karin, M. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042081 · Cited by 252 · see citing works
Lavasani, M., Robinson, A. R., Lu, A., Song, M., Feduska, J. M., Ahani, B., Tilstra, J. S., Feldman, C. H., Robbins, P. D., Niedernhofer, L. J., et al. (2012) · Nature Communications · doi:10.1038/ncomms1611 · Cited by 229 · see citing works
Self-citationSenescence‐associated intrinsic mechanisms of osteoblast dysfunctions
Kassem, M., & Marie, P. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00669.x · Cited by 228 · see citing works
PIASy mediates NEMO sumoylation and NF-κB activation in response to genotoxic stress
Mabb, A. M., Wuerzberger‐Davis, S. M., & Miyamoto, S. (2006) · Nature Cell Biology · doi:10.1038/ncb1458 · Cited by 226 · see citing works
Jaspers, N. G. J., Raams, A., Silengo, M., Wijgers, N., Niedernhofer, L. J., Robinson, A. R., Giglia‐Mari, G., Hoogstraten, D., Kleijer, W. J., Hoeijmakers, J. H. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/512486 · Cited by 213 · see citing works
Self-citationMak, K. K., Bi, Y., Wan, C., Chuang, P.-T., Clemens, T., Young, M., & Yang, Y. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.02.003 · Cited by 202 · see citing works
Physiological consequences of defects in ERCC1–XPF DNA repair endonuclease
Gregg, S. Q., Robinson, A. R., & Niedernhofer, L. J. (2011) · DNA Repair · doi:10.1016/j.dnarep.2011.04.026 · Cited by 175 · see citing works
Self-citationVaira, S., Alhawagri, M., Anwisye, I., Kitaura, H., Faccio, R., & Novack, D. V. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33392 · Cited by 165 · see citing works
Chronic alcohol ingestion induces osteoclastogenesis and bone loss through IL-6 in mice
Dai, J., Lin, D., Zhang, J., Habib, P., Smith, P., Murtha, J., Fu, Z., Yao, Z., Qi, Y., & Keller, E. T. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10483 · Cited by 157 · see citing works
Ink4a/Arf links senescence and aging
Sharpless, N. E. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.06.025 · Cited by 142 · see citing works
Reduced hematopoietic reserves in DNA interstrand crosslink repair‐deficient Ercc1−/− mice
Prasher, J. M., Lalai, A. S., Heijmans‐Antonissen, C., Ploemacher, R., Hoeijmakers, J. H. J., Touw, I. P., & Niedernhofer, L. J. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600542 · Cited by 135 · see citing works
Self-citationMany faces of NF-κB signaling induced by genotoxic stress
Wu, Z., & Miyamoto, S. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0227-9 · Cited by 129 · see citing works
Age-Related Changes in the Osteogenic Differentiation Potential of Mouse Bone Marrow Stromal Cells
Zhang, W., Ou, G., Hamrick, M. W., Hill, W., Borke, J. L., Wenger, K., Chutkan, N. B., Yu, J. C.-K., Mi, Q., Isales, C. M., et al. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.080304 · Cited by 116 · see citing works
Mutational analysis of the human nucleotide excision repair gene ERCC1
Sijbers, A. M. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.17.3370 · Cited by 109 · see citing works
Saeed, H., Abdallah, B. M., Ditzel, N., Catalá-Lehnen, P., Qiu, W., Amling, M., & Kassem, M. S. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.349 · Cited by 107 · see citing works
Broad segmental progeroid changes in short-lived <i>Ercc1</i> <sup>−/Δ7</sup> mice
Dollé, M. E. T., Kuiper, R. V., Roodbergen, M., Robinson, J., de Vlugt, S., Wijnhoven, S. W. P., Beems, R. B., de la Fonteyne, L., de With, P., van der Pluijm, I., et al. (2011) · Pathobiology of Aging & Age-related Diseases · doi:10.3402/pba.v1i0.7219 · Cited by 91 · see citing works
Self-citationEndl, E., & Gerdes, J. (2000) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(200003)182:3 · Cited by 89 · see citing works
Xu, G.-S., Liu, K., Anderson, J. L., Patrene, K., Lentzsch, S., Roodman, G., & Ouyang, H.-J. (2012) · Blood · doi:10.1182/blood-2011-05-353300 · Cited by 75 · see citing works
Self-citationGenetic epidemiology of age-related osteoporosis and its clinical applications
Cheung, C., Xiao, S., & Kung, A. W. (2010) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.106 · Cited by 68 · see citing works
Comparing the yeast retrograde response and NF‐κB stress responses: implications for aging
Srinivasan, V., Kriete, A., Saçan, A., & Jazwinski, S. M. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00622.x · Cited by 61 · see citing works
Tian, M., Jones, D. A., Smith, M., Shinkura, R., & Alt, F. W. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.6.2237-2242.2004 · Cited by 41 · see citing works
Undale, A. H., Srinivasan, B., Drake, M. T., McCready, L. K., Atkinson, E. J., Peterson, J. M., Riggs, B. L., Amin, S., Mödder, U. I., & Khosla, S. (2010) · Bone · doi:10.1016/j.bone.2010.03.018 · Cited by 37 · see citing works
Osteopetrosis with micro-lacunar resorption because of defective integrin organization
Blair, H. C., Yaroslavskiy, B. B., Robinson, L. J., Mapara, M. Y., Pangrazio, A., Guo, L., Chen, K., Vezzoni, P., Tolar, J., & Orchard, P. J. (2009) · Laboratory Investigation · doi:10.1038/labinvest.2009.58 · Cited by 16 · see citing works
Self-citationNF-κB Signature on the Aging Wall
Zineldeen, D. H., Uranishi, H., & Okamoto, T. (2010) · Current Drug Metabolism · doi:10.2174/138920010791196283 · Cited by 12 · see citing works
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- [17]Miyamoto S 2011 Nuclear initiated NF-[kappa]B signaling: NEMO and ATM take center stage Cell Res 21 1 116 130 21187855 PMC3193401
- [49]Chang J Wang Z Tang E Fan Z McCauley L Franceschi R Guan K Krebsbach PH Wang C-Y 2009 Inhibition of osteoblastic bone formation by nuclear factor-[kappa]B Nat Med 15 6 682 689 19448637 PMC2768554
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Guo, J., Huang, X., Dou, L., Yan, M., Shen, T., Tang, W., & Li, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01251-0 · Cited by 1,834 · see citing works
Identification 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 · see citing works
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Pawelec, G., Goldeck, D., & Derhovanessian, E. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.03.007 · Cited by 420 · see citing works
Chang, J., Liu, F., Lee, M., Wu, B. M., Ting, K., Zara, J., Soo, C., Hezaimi, K. A., Zou, W., Chen, X.-H., et al. (2013) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1300532110 · Cited by 317 · see citing works
Characterization of bone marrow-derived mesenchymal stem cells in aging
Baker, N., Boyette, L. B., & Tuan, R. S. (2014) · Bone · doi:10.1016/j.bone.2014.10.014 · Cited by 281 · see citing works
Nuclear genomic instability and aging
Niedernhofer, L. J., Gurkar, A. U., Wang, Y., Vijg, J., Hoeijmakers, J. H. J., & Robbins, P. D. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-012239 · Cited by 275 · see citing works
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Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-κB
Yu, B., Chang, J., Liu, Y., Li, J., Kevork, K., Al‐Hezaimi, K., Graves, D. T., Park, N.-H., & Wang, C. (2014) · Nature Medicine · doi:10.1038/nm.3586 · Cited by 230 · see citing works
Age-related inflammation triggers skeletal stem/progenitor cell dysfunction
Josephson, A. M., Bradaschia-Corrêa, V., Lee, S., Leclerc, K., Patel, K. S., Muiños-López, E., Litwa, H. P., Neibart, S. S., Kadiyala, M. L., Wong, M. Z., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1810692116 · Cited by 205 · see citing works
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Pignolo, R. J., Law, S. F., & Chandra, A. (2021) · JBMR Plus · doi:10.1002/jbm4.10488 · Cited by 206 · see citing works
Kim, H., Chang, J., Shao, L., Han, L., Iyer, S., Manolagas, S. C., O'Brien, C. A., Jilka, R. L., Zhou, D., & Almeida, M. (2017) · Aging Cell · doi:10.1111/acel.12597 · Cited by 192 · see citing works
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García-García, V. A., Alameda, J. P., Page, A., & Casanova, M. (2021) · Cells · doi:10.3390/cells10081906 · Cited by 165 · see citing works
Kalaszczyńska, I., & Ferdyn, K. (2015) · BioMed Research International · doi:10.1155/2015/430847 · Cited by 161 · see citing works
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Hussain, M. S., Altamimi, A. S. A., Afzal, M., Almalki, W. H., Kazmi, I. A., Alzarea, S. I., Gupta, G., Shahwan, M. J., Kukreti, N., Wong, L. S., et al. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112389 · Cited by 145 · see citing works
Luo, H., Gu, R., Ouyang, H., Wang, L., Shi, S., Ji, Y., Bao, B., Liao, G., & Xu, B. (2021) · Environmental Pollution · doi:10.1016/j.envpol.2021.118043 · Cited by 137 · see citing works
Self-citationGenome Integrity in Aging: Human Syndromes, Mouse Models, and Therapeutic Options
Vermeij, W. P., Hoeijmakers, J. H. J., & Pothof, J. (2015) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010814-124316 · Cited by 123 · see citing works
Pathology of mouse models of accelerated aging
Harkema, L., Youssef, S. A., & de Bruin, A. (2016) · Veterinary Pathology · doi:10.1177/0300985815625169 · Cited by 105 · see citing works
Flores, R. R., Clauson, C. L., Cho, J., Lee, B.-C., McGowan, S. J., Baker, D. J., Niedernhofer, L. J., & Robbins, P. D. (2017) · Aging Cell · doi:10.1111/acel.12571 · Cited by 107 · see citing works
Self-citationLi, J., Liu, X., Zuo, B., & Zhang, L. (2016) · Aging and Disease · doi:10.14336/ad.2015.1206 · Cited by 104 · see citing works
Cellular senescence and the skeleton: pathophysiology and therapeutic implications
Khosla, S., Farr, J. N., & Monroe, D. G. (2022) · Journal of Clinical Investigation · doi:10.1172/jci154888 · Cited by 104 · see citing works
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Self-citationColaianni, G., Errede, M., Sanesi, L., Notarnicola, A., Celi, M., Zerlotin, R., Storlino, G., Pignataro, P., Oranger, A., Pesce, V., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4192 · Cited by 69 · see citing works
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NF-κB signaling as a driver of ageing
Osorio, F. G., Soria‐Valles, C., Santiago‐Fernández, O., Freije, J. M. P., & López-Otı́n, C. (2016) · International review of cytology · doi:10.1016/bs.ircmb.2016.04.003 · Cited by 67 · see citing works
Kim, D. E., Dollé, M. E. T., Vermeij, W. P., Gyenis, Á., Vogel, K., Hoeijmakers, J. H. J., Wiley, C. D., Davalos, A. R., Hasty, P., Desprez, P., et al. (2019) · Aging Cell · doi:10.1111/acel.13072 · Cited by 64 · see citing works
Zhang, P., Liu, Y., Jin, C., Zhang, M., Tang, F., & Zhou, Y. (2015) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2704 · Cited by 64 · see citing works
Bolderson, E., Burgess, J. T., Li, J., Gandhi, N. S., Boucher, D., Croft, L. V., Beard, S., Plowman, J., Suraweera, A., Adams, M. N., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13167-5 · Cited by 60 · see citing works
Genome Instability and DNA Repair in Somatic and Reproductive Aging
Panier, S., Wang, S., & Schumacher, B. (2023) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-051122-093128 · Cited by 60 · see citing works
DNA damage in aging, the stem cell perspective
McNeely, T., Leone, M., Yanai, H., & Beerman, I. (2020) · Human Genetics · doi:10.1007/s00439-019-02047-z · Cited by 52 · see citing works
“NER (Ercc1−/−/Ercc1−/Δ) Accelerated osteoporosis accompanied by progenitor senescence and accumulation of DNA damage Chen et al. (2013), Niedernhofer et al. (2006)”
BackgroundInfluentialSenescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype
Ngo, K., Patil, P. R., McGowan, S. J., Niedernhofer, L. J., Robbins, P. D., Kang, J. D., Sowa, G., & Vo, N. N. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.08.007 · Cited by 52 · see citing works
Self-citationAge-associated changes in the ecological niche: implications for mesenchymal stem cell aging
Asumda, F. Z. (2013) · Stem Cell Research & Therapy · doi:10.1186/scrt197 · Cited by 51 · see citing works
Despars, G., Carbonneau, C. L., Bardeau, P., Coutu, D. L., & Beausejour, C. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073206 · Cited by 48 · see citing works
Regulatory mechanisms and clinical manifestations of musculoskeletal aging
Grote, C. W., Reinhardt, D., Zhang, M., & Wang, J. (2019) · Journal of Orthopaedic Research® · doi:10.1002/jor.24292 · Cited by 53 · see citing works
Mouse Models of Accelerated Cellular Senescence
Yousefzadeh, M. J., Melos, K. I., Angelini, L. A., Burd, C. E., Robbins, P. D., & Niedernhofer, L. J. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8931-7_17 · Cited by 47 · see citing works
Self-citationA tale of the good and bad: Cell senescence in bone homeostasis and disease
Liu, X., & Wan, M. (2019) · International review of cytology · doi:10.1016/bs.ircmb.2019.03.005 · Cited by 44 · see citing works
HO-1 in Bone Biology: Potential Therapeutic Strategies for Osteoporosis
Zhou, X., Yuan, W., Xiong, X., Zhang, Z., Liu, J., Zheng, Y., Wang, J., & Liu, J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.791585 · Cited by 45 · see citing works
A dual role of HIF1α in regulating osteogenesis–angiogenesis coupling
Shao, J., Liu, S., Zhang, M., Chen, S., Gan, S., Chen, C., Chen, W., Li, L., & Zhu, Z. M. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02742-1 · Cited by 42 · see citing works
Messer, J. G., Hopkins, R. G., & Kipp, D. E. (2015) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25141 · Cited by 40 · see citing works
Impaired autophagy triggered by HDAC9 in mesenchymal stem cells accelerates bone mass loss
Zhang, L., Qi, M., Chen, J., Zhao, J., Li, L., Hu, J.-C. E., Jin, Y. J., & Liu, W. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01785-6 · Cited by 38 · see citing works
Xu, Y., Hu, X., Cai, J., Li, Y., Zou, Y., Wang, Y., Xie, C., Xu, S., Wang, Y., Zheng, Y., et al. (2023) · Phytotherapy Research · doi:10.1002/ptr.7929 · Cited by 35 · see citing works
Murine models of accelerated aging and musculoskeletal disease
Hambright, W. S., Niedernhofer, L. J., Huard, J., & Robbins, P. D. (2019) · Bone · doi:10.1016/j.bone.2019.03.002 · Cited by 32 · see citing works
Self-citationRejuvenation 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
Yilmaz, D., Mathavan, N., Wehrle, E., Kuhn, G. A., & Müller, R. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102118 · Cited by 34 · see citing works
GIT2—A keystone in ageing and age-related disease
van Gastel, J., Boddaert, J., Jushaj, A., Premont, R. T., Luttrell, L. M., Janssens, J., Martin, B., & Maudsley, S. R. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.02.002 · Cited by 32 · see citing works
Takayama, K., Kawakami, Y., Lavasani, M., Mu, X., Cummins, J. H., Yurube, T., Kuroda, R., Kurosaka, M., Fu, F. H., Robbins, P. D., et al. (2016) · Journal of Orthopaedic Research® · doi:10.1002/jor.23409 · Cited by 31 · see citing works
Self-citationLiu, X., Li, Z., Liu, H., Zhu, Y., Xia, D., Wang, S., Gu, R., Wu, W., Zhang, P., Liu, Y., et al. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1321-y · Cited by 26 · see citing works
Pignolo, R. J. (2023) · Comprehensive physiology · doi:10.1002/j.2040-4603.2023.tb00253.x · Cited by 21 · see citing works
The multifaceted roles of DNA repair and replication proteins in aging and obesity
D’Amico, A. M., & Vásquez, K. M. (2021) · DNA repair · doi:10.1016/j.dnarep.2021.103049 · Cited by 21 · see citing works
Age‐related dystrophic changes in corneal endothelium from DNA repair–deficient mice
Roh, D. S., Du, Y., Gabriele, M. L., Robinson, A. R., Niedernhofer, L. J., & Funderburgh, J. L. (2013) · Aging Cell · doi:10.1111/acel.12143 · Cited by 21 · see citing works
Self-citationERCC1-deficient cells and mice are hypersensitive to lipid peroxidation
Czerwińska, J., Nowak, M., Wojtczak, P., Dziuban-Lech, D., Cieśla, J., Kołata, D., Gajewska, B., Barańczyk‐Kuźma, A., Robinson, A. R., Shane, H. L., et al. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.05.088 · Cited by 20 · see citing works
Self-citationMolecular Interactions between Dietary Lipids and Bone Tissue during Aging
Romero‐Márquez, J. M., Varela‐López, A., Navarro‐Hortal, M. D., Badillo-Carrasco, A., Forbes-Hernández, T. Y., Giampieri, F., Azpíroz, I. D., Madrigal, L., Battino, M. A., & Quiles, J. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126473 · Cited by 20 · see citing works
Suppression effect of N-acetylcysteine on bone loss in ovariectomized mice.
Zhou, X., Wang, Z., Ni, Y.-H., Yu, Y., Wang, G., & Chen, L. (2020) · PubMed Central · Cited by 19 · see citing works
Stem Cell Secretome for Spinal Cord Repair: Is It More than Just a Random Baseline Set of Factors?
Pajer, K., Bellák, T., & Nógrádi, A. (2021) · Cells · doi:10.3390/cells10113214 · Cited by 19 · see citing works
Pignolo, R. J. (2023) · Comprehensive physiology · doi:10.1002/cphy.c220012 · Cited by 42 · see citing works
Alterations in the microenvironment and the effects produced of TRPV5 in osteoporosis
Luo, Z.-H., Ma, J., Zhang, W., Tian, A., Gong, S.-W., Yan, L., Lai, Y., & Ma, X. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04182-8 · Cited by 17 · see citing works
Zeng, L., Sun, C., Pei, Z., Yun, T., Fan, S., Long, S., Wu, T., Chen, Z., Zhi-min, Y., & Xu, F. (2019) · Biogerontology · doi:10.1007/s10522-019-09820-7 · Cited by 17 · see citing works
Whole chromosome aneuploidy in the brain of Bub1bH/Hand Ercc1−/Δ7mice
Andriani, G. A., Faggioli, F., Baker, D. J., Dollé, M. E. T., Sellers, R. S., Hébert, J. M., STEEG, H. V., Hoeijmakers, J. H. J., Vijg, J., & Montagna, C. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv612 · Cited by 16 · see citing works
Osteoblast versus Adipocyte: Bone Marrow Microenvironment-Guided Epigenetic Control
Li, J., Zuo, B., Zhang, L., Dai, L., & Zhang, X. (2018) · Case Reports in Orthopedic Research · doi:10.1159/000489053 · Cited by 16 · see citing works
Cereblon (CRBN) deletion reverses streptozotocin induced diabetic osteoporosis in mice
Yao, C., Guo, X., Yao, W., & Zhang, C. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.01.095 · Cited by 17 · see citing works
Wu, H., Zhang, Q., Zhu, J., Wu, L., Xiao, Y., & Yang, X. (2025) · Bioactive Materials · doi:10.1016/j.bioactmat.2025.09.002 · Cited by 17 · see citing works
Wei, W., Qi, X., Cheng, B., Zhang, N., Zhao, Y., Qin, X., He, D., Chu, X., Shi, S., Cai, Q., et al. (2024) · Communications Medicine · doi:10.1038/s43856-024-00706-5 · Cited by 15 · see citing works
Lee, H., Lee, H., Na, C., Song, I., Ryu, J., & Park, J. (2021) · Medicina · doi:10.3390/medicina57060520 · Cited by 14 · see citing works
Wang, S., Zhai, J., Heng, K., Sha, L., Song, X., Zhai, H., Dai, C., Li, J., Teng, F., Huang, J., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-82262-5 · Cited by 12 · see citing works
Chandra, A., Law, S. F., & Pignolo, R. J. (2025) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2025.112059 · Cited by 13 · see citing works
Nicholson, T. A., Davis, L. C., Davis, E. T., Ede, M. N., Scott, A., & Jones, S. W. (2022) · Toxics · doi:10.3390/toxics10090506 · Cited by 12 · see citing works
Irie, K., Tomofuji, T., Ekuni, D., Fukuhara, D., Uchida, Y., Kataoka, K., Kobayashi, S., Kikuchi, T., Mitani, A., Shimazaki, Y., et al. (2017) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2017.12.007 · Cited by 12 · see citing works
Pieren, D. K. J., Smits, N. A. M., Imholz, S., Nagarajah, B., van Oostrom, C. T., Brandt, R. M. C., Vermeij, W. P., Dollé, M. E. T., & Guichelaar, T. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.667193 · Cited by 11 · see citing works
Deciphering Osteosarcopenia through the hallmarks of aging
Franulic, F., Salech, F., Rivas, D., & Duque, G. (2024) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2024.111997 · Cited by 13 · see citing works
Rahman, F. A. (2021) · BDJ Open · doi:10.1038/s41405-021-00090-5 · Cited by 11 · see citing works
Mukherjee, S., Park, J. P., & Yun, J. W. (2022) · Biotechnology and Bioprocess Engineering · doi:10.1007/s12257-021-0133-y · Cited by 10 · see citing works
Skeletal phenotypes and molecular mechanisms in aging mice
Guan, Q., 上海体育大学运动健康学院, 上. 2., Zhang, Y., Wang, Z., Liu, X.-H., Zou, J., & Zhang, L.-L. (2024) · 动物学研究 · doi:10.24272/j.issn.2095-8137.2023.397 · Cited by 11 · see citing works
Sasaki, Y., Nakatsuka, R., Inouchi, T., Masutani, M., & Nozaki, T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23095041 · Cited by 9 · see citing works
Aging, Cellular Senescence, and Kidney Fibrosis
Susnik, N., Sen, P., Melk, A., & Schmitt, R. (2017) · Current Pathobiology Reports · doi:10.1007/s40139-017-0143-9 · Cited by 9 · see citing works
Cellular senescence and aging in bone
Mohan, M., Muthusami, S., Selvamurugan, N., Narasimhan, S., Kumaran, R., & Ramachandran, I. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820071-1.00013-x · Cited by 8 · see citing works
Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis
Liu, L., Liu, Z.-R., Cao, L.-J., Wang, J., Huang, S.-M., Hu, S.-G., Yang, Y.-Z., Li, D., Cao, W.-W., Zeng, Q.-B., et al. (2024) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-024-04535-z · Cited by 8 · see citing works
Soper, R., Oguz, C., Emery, R. J., Pitsillides, A. A., & Hodges, S. J. (2014) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201400063 · Cited by 8 · see citing works
Wu, X., Liang, S., Zhu, X., Wu, X., & Zhan, D. (2020) · PubMed Central · Cited by 8 · see citing works
Weng, K., He, Y., Weng, X., & Yuan, Y. J. (2025) · Bone · doi:10.1016/j.bone.2025.117485 · Cited by 7 · see citing works
Skeletal stem cells and their contribution to skeletal fragility: senescence and rejuvenation
Aldahmash, A. M. (2015) · Biogerontology · doi:10.1007/s10522-015-9623-7 · Cited by 8 · see citing works
Zhang, Z., Zhou, C., & Yu, L. (2024) · BMC Molecular and Cell Biology · doi:10.1186/s12860-024-00523-7 · Cited by 6 · see citing works
Chemotherapy-induced adipo-lineage cell senescence drives bone loss
Raut, G., Malachowski, T., Melam, A., Ramalho-Oliveira, R., Holt, T., Luo, X.-M., Yao, Z.-T., Faget, D. V., Ren, Q.-H., DeNardo, D., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-67793-3 · Cited by 8 · see citing works
Musculoskeletal Health of the Adults Over 50 Years of Age in Relation to Antioxidant Vitamin Intakes
Kim, N., Kang, Y., Choi, Y. J., Lee, Y., Park, S. J., Park, H. S., Kwon, M., Chung, Y., & Park, Y. K. (2022) · Clinical Nutrition Research · doi:10.7762/cnr.2022.11.2.84 · Cited by 6 · see citing works
Usategui‐Martín, R., Gutiérrez-Cerrajero, C., Jiménez-Vázquez, S., Calero‐Paniagua, I., García‐Aparicio, J., Corral-Gudino, L., del Pino‐Montes, J., & González‐Sarmiento, R. (2018) · Bone · doi:10.1016/j.bone.2018.04.003 · Cited by 6 · see citing works
Ji, X., Chen, H., Liu, B., Zhuang, H., & Bu, S. (2023) · PubMed Central · Cited by 6 · see citing works
Wu, H., Wu, J., & Wen, G. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1605473 · Cited by 5 · see citing works
Aging mitochondria in the context of SARS-CoV-2: exploring interactions and implications
Delpino, M. V., & Quarleri, J. F. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1442323 · Cited by 5 · see citing works
Liu, Y., Ji, X., Zhang, J., Lü, J., Liu, B., Sun, H., & Miao, D. (2025) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2025.04.014 · Cited by 6 · see citing works
A View of Myeloid Transformation through the Hallmarks of Cancer
Fernández-Maestre, I., Cai, S. F., & Levine, R. L. (2024) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-24-0009 · Cited by 4 · see citing works
- Authors
- Chen, Q., Liu, K., Robinson, A. R., Clauson, C. L., Blair, H. C., Robbins, P. D., Niedernhofer, L. J., & Ouyang, H.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Ouyang, Hongjiao
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-12-21
- Volume
- 28
- Issue
- 5
- Pages
- 1214-1228
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- PMC
- PMC3662975
- OpenAlex
- W2052845629
- Cited by
- 135
- References
- 52
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 16 · 2023: 12 · 2022: 9 · 2021: 16 · 2020: 5 · 2019: 13 · 2018: 8 · 2017: 5 · 2016: 9 · 2015: 8 · 2014: 7 · 2013: 5
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Ellison Medical Foundation (P30CA047904, AG-NS-0303-05, P30AG024827, ES016114)
- Multiple Myeloma Research Foundation
- Scoliosis Research Society
- University of Pittsburgh (P30-AG024827, P30 CA047904)
- National Institutes of Health (AG-NS-0303-05, AG024827)
- VA Pittsburgh Healthcare System
- National Institute on Aging (R21AG033907, AG 024827, AG033907, P30AG024827)
- National Cancer Institute (ES016114, R21CA161150, P30CA047904)
- National Institute of Neurological Disorders and Stroke (U01NS058451, NS058451)
- National Institute of Environmental Health Sciences (ES 016114, R01ES016114)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR051456, R01AR055208, R01AR051456)
- National Institute of Dental and Craniofacial Research (R01DE017439)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- DNA damage, bone aging, osteoporosis, NF-κB signaling, ERCC1, progeroid syndromes, cellular senescence, senescence-associated secretory phenotype, mesenchymal stem cells, osteoclastogenesis, bone formation, IKK inhibitor, NF-κB p65, inflammatory cytokines, RANKL
- MeSH terms
- Animals, Bone and Bones, Cell Differentiation, Cells, Cultured, DNA Damage, DNA-Binding Proteins, Endonucleases, Osteoblasts, Osteoporosis, NF-kappa B, Mice, Knockout, Mice
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