DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age
Open accessAbstract
Summary Age‐related bone loss in mice results from a decrease in bone formation and an increase in cortical bone resorption. The former is accounted by a decrease in the number of postmitotic osteoblasts which synthesize the bone matrix and is thought to be the consequence of age‐dependent changes in mesenchymal osteoblast progenitors. However, there are no specific markers for these progenitors, and conclusions rely on results from in vitro cultures of mixed cell populations. Moreover, the culprits of such changes remain unknown. Here, we have used Osx1‐Cre;TdRFP mice in which osteoprogenitors express the TdRFP fluorescent protein. We report that the number of TdRFP‐Osx1 cells, freshly isolated from the bone marrow, declines by more than 50% between 6 and 24 months of age in both female and male mice. Moreover, TdRFP‐Osx1 cells from old mice exhibited markers of DNA damage and senescence, such as γH2AX foci, G1 cell cycle arrest, phosphorylation of p53, increased p21CIP1 levels, as well as increased levels of GATA4 and activation of NF‐κB – two major stimulators of the senescence‐associated secretory phenotype (SASP). Bone marrow stromal cells from old mice also exhibited elevated expression of SASP genes, including several pro‐osteoclastogenic cytokines, and increased capacity to support osteoclast formation. These changes were greatly attenuated by the senolytic drug ABT263. Together, these findings suggest that the decline in bone mass with age is the result of intrinsic defects in osteoprogenitor cells, leading to decreased osteoblast numbers and increased support of osteoclast formation.
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Senescent cells play an important role in skeletal aging in part by decreasing osteoprogenitor cell number and the generation of osteoblasts that produce the bone matrix, and by stimulating osteoclastogenesis to resorb the bone.
“Recent studies by us and others have shown that SCs play an important role in skeletal aging in part by decreasing osteoprogenitor cell number and the generation of osteoblasts that produce the bone matrix; stimulate osteoclastogenesis to resorb the bone42,43.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [42]
PZ might be slightly more effective than ABT263 in clearance of senescent BM osteoblast progenitors in naturally aged mice because these progenitors undergo senescence in a p21-dependent, but p16-independent, manner.
“This result suggests that PZ might be slightly more effective than ABT263 in clearance of senescent BM osteoblast progenitors in naturally aged mice because these progenitors undergo senescence in a p21-dependent, but p16-independent, manner42.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [42]
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Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 2× · see citing works
“…with evidence that removal of senescent cells via genetic or pharmacologic means attenuates the age-dependent degeneration of several tissues (Baker et al., 2011, 2016; Chang et al., 2016), the present work supports the notion that removal of senescent cells may represent a therapeutic…”
BackgroundAging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · see citing works
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,891 · see citing works
The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623 · see citing works
Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone
Kusumbe, A. P., Ramasamy, S. K., & Adams, R. H. (2014) · Nature · doi:10.1038/nature13145 · Cited by 2,155 · see citing works
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · see citing works
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4010 · Cited by 1,819 · see citing works
Self-citationWeinstein, R. S., Jilka, R. L., Parfitt, A. M., & Manolagas, S. C. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2799 · Cited by 1,753 · cited 1× · see citing works
“Because osteoblasts are postmitotic cells with a short lifespan (Weinstein et al., 1998), they need to be constantly replaced with new ones.”
BackgroundSelf-citationp53 mutant mice that display early ageing-associated phenotypes
Tyner, S. D., Venkatachalam, S., Choi, J., Jones, S., Ghebranious, N., Igelmann, H., Lu, X., Soron, G., Cooper, B., Brayton, C., et al. (2002) · Nature · doi:10.1038/415045a · Cited by 1,459 · cited 2× · see citing works
“transgenic mice with global gain-of-function mutation of p53 rapidly accumulate senescent cells and exhibit accelerated aging phenotypes, including low bone mass (Tyner et al., 2002; Maier et al., 2004).”
BackgroundHerbig, U., Jobling, W. A., Chen, B. P. C., Chen, D. J., & Sedivy, J. M. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00256-4 · Cited by 1,344 · cited 1× · see citing works
“An increase in p21 levels due to p53 activation is a critical mediator of cell cycle arrest and senescence following DNA damage in several cell types (Herbig et al., 2004; Passos et al., 2010).”
BackgroundMatrix-embedded cells control osteoclast formation
Xiong, J., Onal, M., Jilka, R. L., Weinstein, R. S., Manolagas, S. C., & O'Brien, C. A. (2011) · Nature Medicine · doi:10.1038/nm.2448 · Cited by 1,304 · see citing works
Self-citationStenderup, K. (2003) · Bone · doi:10.1016/j.bone.2003.07.005 · Cited by 1,207 · see citing works
Cellular Senescence in Aging Primates
Herbig, U., Ferreira, M., Condel, L., Carey, D., & Sedivy, J. M. (2006) · Science · doi:10.1126/science.1122446 · Cited by 1,101 · see citing works
Expression of Cre recombinase in the developing mouse limb bud driven by a Prxl enhancer
Logan, M., Martin, J. F., Nagy, A., Lobe, C., Olson, E., & Tabin, C. (2002) · Genesis · doi:10.1002/gene.10092 · Cited by 1,022 · see citing works
Feedback between p21 and reactive oxygen production is necessary for cell senescence
Passos, J. F., Nelson, G., Wang, C., Richter, T., Simillion, C., Proctor, C. J., Miwa, S., Olijslagers, S., Hallinan, J., Wipat, A., et al. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.5 · Cited by 1,019 · cited 1× · see citing works
“An increase in p21 levels due to p53 activation is a critical mediator of cell cycle arrest and senescence following DNA damage in several cell types (Herbig et al., 2004; Passos et al., 2010).”
BackgroundRodda, S. J., & McMahon, A. P. (2006) · Development · doi:10.1242/dev.02480 · Cited by 1,011 · see citing works
The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4.
Kang, C., Xu, Q., Martin, T. D., Li, M. Z., Demaria, M., Aron, L., Lu, T., Yankner, B. A., Campisi, J., & Elledge, S. J. (2015) · Science · doi:10.1126/science.aaa5612 · Cited by 982 · see citing works
Stems Cells and the Pathways to Aging and Cancer
Rossi, D. J., Jamieson, C. H. M., & Weissman, I. L. (2008) · Cell · doi:10.1016/j.cell.2008.01.036 · Cited by 895 · see citing works
Zhou, S., Greenberger, J. S., Epperly, M. W., Goff, J. P., Adler, C., LeBoff, M. S., & Glowacki, J. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00377.x · Cited by 782 · see citing works
Skeletal Involution by Age-associated Oxidative Stress and Its Acceleration by Loss of Sex Steroids
Almeida, M., Li, H., Martín-Millán, M., Plotkin, L. I., Stewart, S. A., Roberson, P. K., Kousteni, S., O’Brien, C. A., Bellido, T., PARFITT, A. M., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702810200 · Cited by 707 · see citing works
Self-citationDNA 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
Park, D., Spencer, J. A., Koh, B. I., Kobayashi, T., Fujisaki, J., Clemens, T. L., Lin, C. P., Kronenberg, H. M., & Scadden, D. T. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.02.003 · Cited by 627 · see citing works
Aging of mesenchymal stem cells
Sethe, S. C., Scutt, A. M., & Stolzing, A. (2005) · Ageing Research Reviews · doi:10.1016/j.arr.2005.10.001 · Cited by 615 · see citing works
Modulation of mammalian life span by the short isoform of p53
Maier, B., Gluba, W., Bernier, B., Turner, T., Mohammad, K., Guise, T., Sutherland, A., Thorner, M., & Scrable, H. (2004) · Genes & Development · doi:10.1101/gad.1162404 · Cited by 586 · 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
Rodier, F., Muñoz, D. P., Teachenor, R., Chu, V., Le, O., Bhaumik, D., Coppé, J.-P., Campeau, E., Beauséjour, C. M., Kim, S.-H., et al. (2011) · Journal of Cell Science · doi:10.1242/jcs.071340 · Cited by 535 · see citing works
Robles, S. J., & Adami, G. R. (1998) · Oncogene · doi:10.1038/sj.onc.1201862 · Cited by 498 · see citing works
Luche, H., Weber, O., Nageswara Rao, T., Blum, C., & Fehling, H. J. (2007) · European Journal of Immunology · doi:10.1002/eji.200636745 · Cited by 482 · see citing works
Pfeilschifter, J., Chenu, C., Bird, A., Mundy, G. R., & Roodman, D. (1989) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650040116 · Cited by 468 · see citing works
Roninson, I. B. (2002) · Cancer Letters · doi:10.1016/s0304-3835(01)00847-3 · Cited by 443 · see citing works
Itahana, K., Bhat, K., Jin, A., Itahana, Y., Hawke, D. H., Kobayashi, R., & Zhang, Y. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00431-3 · Cited by 431 · see citing works
Deletion of Ku86 causes early onset of senescence in mice
Vogel, H., Lim, D.-S., Karsenty, G., Finegold, M., & Hasty, P. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.19.10770 · Cited by 368 · see citing works
Hematopoietic Stem Cell Injury Induced by Ionizing Radiation
Shao, L., Luo, Y., & Zhou, D. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5635 · Cited by 337 · see citing works
Self-citationCoppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · see citing works
Osteoblast differentiation and skeletal development are regulated by Mdm2–p53 signaling
Lengner, C. J., Steinman, H. A., Gagnon, J. A., Smith, T. W., Henderson, J. E., Kream, B. E., Stein, G. S., Lian, J. B., & Jones, S. N. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200508130 · Cited by 266 · see citing works
Wang, X., Kua, H.-Y., Hu, Y., Guo, K., Zeng, Q., Wu, Q., Ng, H., Karsenty, G., Crombrugghe, B. D., Yeh, J. K., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200507106 · Cited by 250 · see citing works
Wright, L. M., Maloney, W. J., YU, X., Kindle, L., Collin‐Osdoby, P., & Osdoby, P. (2005) · Bone · doi:10.1016/j.bone.2005.01.021 · Cited by 231 · see citing works
Parfitt, A. M., Villanueva, A. R., Foldes, J., & Rao, D. S. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650100319 · Cited by 231 · see citing works
Senescence‐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
Ionizing Radiation-Induced Endothelial Cell Senescence and Cardiovascular Diseases
Wang, Y., Boerma, M., & Zhou, D. (2016) · Radiation Research · doi:10.1667/rr14445.1 · Cited by 204 · see citing works
Self-citationBasic Biology of Skeletal Aging: Role of Stress Response Pathways
Almeida, M., & O’Brien, C. A. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt079 · Cited by 202 · see citing works
Self-citationDNA damage response in adult stem cells: pathways and consequences
Mandal, P. K., Blanpain, C., & Rossi, D. J. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3060 · Cited by 195 · see citing works
Cao, J., Wronski, T. J., Iwaniec, U. T., Phleger, L., Kurimoto, P., Boudignon, B. M., & Halloran, B. P. (2005) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.050503 · Cited by 195 · see citing works
Regulation of growth arrest in senescence: Telomere damage is not the end of the story
Herbig, U., & Sedivy, J. M. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.09.002 · Cited by 159 · see citing works
Stromal-Initiated Changes in the Bone Promote Metastatic Niche Development
Luo, X., Fu, Y., Loza, A. J., Murali, B., Leahy, K. M., Ruhland, M. K., Gang, M., Su, X., Zamani, A., Shi, Y., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.016 · Cited by 141 · see citing works
DNA damage drives accelerated bone aging via an NF- <b>κ</b> B–dependent mechanism
Chen, Q., Liu, K., Robinson, A. R., Clauson, C. L., Blair, H. C., Robbins, P. D., Niedernhofer, L. J., & Ouyang, H. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1851 · Cited by 135 · see citing works
Ucer, S., Iyer, S. V., Kim, H., Han, L., Rutlen, C., Allison, K. C., Thostenson, J. D., de Cabo, R., Jilka, R. L., O’Brien, C. A., et al. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3014 · Cited by 116 · see citing works
Self-citationChandra, A., Lin, T., Young, T. J., Tong, W., Ma, X., Tseng, W., Krämer, I., Kneissel, M., Levine, M. A., Zhang, Y., et al. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2996 · Cited by 110 · 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
Sui, B., Hu, C., Liao, L., Chen, Y., Zhang, X., Fu, X., Zheng, C., Li, M., Wu, L., Zhao, X., et al. (2016) · Scientific Reports · doi:10.1038/srep30186 · Cited by 88 · see citing works
Jilka, R. L., O’Brien, C. A., Roberson, P. K., Bonewald, L. F., Weinstein, R. S., & Manolagas, S. C. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2007 · Cited by 85 · see citing works
Self-citationMultiple myeloma–derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease
Fu, J., Li, S., Feng, R., Ma, H., Sabeh, F., Roodman, G. D., Wang, J., Robinson, S. T., Guo, X.-D. E., Lund, T., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci80276 · Cited by 76 · see citing works
p21WAF1/CIP1 Acts as a Brake in Osteoblast Differentiation
Bellosta, P., Masramon, L., Mansukhani, A., & Basilico, C. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.5.818 · Cited by 56 · see citing works
GATA4 Is Essential for Bone Mineralization via ERα and TGFβ/BMP Pathways
Güemes, M., Garcia, A. J., Rigueur, D., Runke, S., Wang, W., Zhao, G., Mayorga, V. H., Atti, E., Tetradis, S., Péault, B., et al. (2014) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2296 · Cited by 43 · see citing works
White, R. R., Sung, P., Vestal, C. G., Benedetto, G., Cornelio, N., & Richardson, C. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084379 · Cited by 22 · see citing works
Mesenchymal Progenitor Cells for the Osteogenic Lineage
Ono, N., & Kronenberg, H. M. (2015) · Current Molecular Biology Reports · doi:10.1007/s40610-015-0017-z · Cited by 20 · see citing works
GATA4 negatively regulates osteoblast differentiation by downregulation of Runx2
Song, I., Kim, K., Kim, J. H., Lee, Y., Jung, H.-J., Byun, H., Yoon, G., & Kim, N. (2014) · BMB Reports · doi:10.5483/bmbrep.2014.47.8.225 · Cited by 20 · see citing works
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Kritsilis, M., V. Rizou, S., Koutsoudaki, P. N., Evangelou, K., Gorgoulis, V. G., & Papadopoulos, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102937 · Cited by 448 · see citing works
He, Y., Zhang, X., Chang, J., Kim, H.-N., Zhang, P., Wang, Y., Khan, S., Liu, X., Zhang, X., Lv, D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15838-0 · Cited by 280 · see citing works
Self-citationFarr, J. N., & Khosla, S. (2019) · Bone · doi:10.1016/j.bone.2019.01.015 · Cited by 263 · see citing works
Connective tissue and fibroblast senescence in skin aging
Wlaschek, M., Maity, P., Makrantonaki, E., & Scharffetter-Kochanek, K. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.11.010 · Cited by 245 · see citing works
The Cancer SENESCopedia: A delineation of cancer cell senescence
Jochems, F., Thijssen, B., De Conti, G., Jansen, R., Pogacar, Z., Groot, K., Wang, L., Schepers, A., Wang, C., Jin, H., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109441 · Cited by 201 · see citing works
Gnani, D., Crippa, S., della Volpe, L., Rossella, V., Conti, A., Lettera, E., Rivis, S., Ometti, M., Fraschini, G., Bernardo, M. E., et al. (2019) · Aging Cell · doi:10.1111/acel.12933 · Cited by 188 · see citing works
Senescence and senotherapeutics: a new field in cancer therapy
Myrianthopoulos, V., Evangelou, K., Vasileiou, P. V. S., Cooks, T., Vassilakopoulos, T. P., Pangalis, G. A., Kouloukoussa, M., Kittas, C., Georgakilas, A. G., & Gorgoulis, V. G. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.08.006 · Cited by 160 · see citing works
Lozano-Torres, B., Estepa-Fernández, A., Rovira, M., Orzáez, M., Serrano, M., Martínez-Máñez, R., & Sancenón, F. (2019) · Nature Reviews Chemistry · doi:10.1038/s41570-019-0108-0 · Cited by 140 · see citing works
Inhibiting Cellular Senescence: A New Therapeutic Paradigm for Age-Related Osteoporosis
Khosla, S., Farr, J. N., & Kirkland, J. L. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-02694 · Cited by 130 · see citing works
Sharma, A. K., Roberts, R. L., Benson, R. D., Pierce, J. L., Yu, K., Hamrick, M. W., & McGee-Lawrence, M. E. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00354 · Cited by 131 · see citing works
“…that is commonly added to osteogenic cultures at low dosages (e.g., 100 nM) to enhance osteoblastic differentiation (Yamanouchi et al., 2001; Langenbach and Handschel, 2013; Yuasa et al., 2015), but can also affect osteoblastic cell metabolism and apoptosis particularly at higher…”
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Ali, D., Tencerova, M., Figeac, F., Kassem, M., & Jafari, A. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.981487 · Cited by 122 · see citing works
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Bai, J., Wang, Y., Wang, J., Zhai, J., He, F., & Zhu, G. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00520.2019 · Cited by 72 · see citing works
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- Authors
- Kim, H., Chang, J., Shao, L., Han, L., Iyer, S., Manolagas, S. C., O'Brien, C. A., Jilka, R. L., Zhou, D., & Almeida, M.
- Affiliations
- Central Arkansas Veterans Healthcare System (US)
- University of Arkansas for Medical Sciences (US)
- Division of Endocrinology and Metabolism Center for Osteoporosis and Metabolic Bone Diseases University of Arkansas for Medical Sciences Little Rock AR USA
- Corresponding author
- Almeida, Maria
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2017-04-12
- Volume
- 16
- Issue
- 4
- Pages
- 693-703
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC5506444
- OpenAlex
- W2606663768
- Cited by
- 192
- References
- 62
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 17 · 2023: 17 · 2022: 25 · 2021: 39 · 2020: 23 · 2019: 24 · 2018: 16 · 2017: 3
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01 AR56679, R01 CA122023, P01 AG13918)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- osteoprogenitor cells, cellular senescence, DNA damage, age-related bone loss, mesenchymal stem cells, senescence-associated secretory phenotype, osteoclastogenesis, osteoblast progenitors, p53, GATA4, NF-κB, senolytics, navitoclax, G1 cell cycle arrest
- MeSH terms
- Sp7 Transcription Factor, Red Fluorescent Protein, Aging, Aniline Compounds, Animals, Bone and Bones, Cell Differentiation, DNA Damage, Female, Gene Expression Regulation, Histones, Luminescent Proteins, Male, Mice, Transgenic, Osteoblasts, Osteoclasts, Osteogenesis, Osteoporosis, Sulfonamides, Signal Transduction, Tumor Suppressor Protein p53, NF-kappa B, Genes, Reporter, Cyclin-Dependent Kinase Inhibitor p21, GATA4 Transcription Factor, Mice, G1 Phase Cell Cycle Checkpoints, Mesenchymal Stem Cells, Primary Cell Culture
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 ›
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