Mouse models of telomere dysfunction phenocopy skeletal changes found in human age-related osteoporosis
Open accessAbstract
A major challenge in the elderly is osteoporosis and the high risk of fracture. Telomere dysfunction is a cause of cellular senescence and telomere shortening which occurs with age in cells from most human tissues, including bone. Telomere defects contribute to the pathogenesis of two progeroid disorders characterized by premature osteoporosis, Werner syndrome and dyskeratosis congenital. It is hypothesized that telomere shortening contributes to bone aging. Using mice with disrupted telomere maintenance mechanisms, including mutants in Werner helicase (Wrn-/-), telomerase (Terc-/-) and Wrn-/- Terc-/- double mutants, we evaluated their skeletal phenotypes as models for human bone aging. Compared to young wild-type (WT) mice, micro-computerized tomography analysis revealed that young Terc-/- and Wrn-/-Terc-/- mice have decreased trabecular bone volume, trabecular number and trabecular thickness, as well as increased trabecular spacing. In cortical bone, young Terc-/- and Wrn-/-Terc-/- mice have increased cortical thinning, and increased porosity relative to age-matched WT mice. These trabecular and cortical changes were accelerated with age in Terc-/- and Wrn-/-Terc-/- mice compared to older WT mice. Histological quantification of osteoblasts in aged mice showed a similar number of osteoblasts in all genotypes; however, significant decreases in osteoid, mineralization surface, mineral apposition rate and bone formation rate in older Terc-/- and Wrn-/-Terc-/- bone suggest that osteoblast dysfunction is a prominent feature of precocious aging in these mice. Except in the Wrn-/- single mutant, osteoclast number did not increase in any genotype. Significant alterations in mechanical parameters (structure model index, degree of anistrophy, and moment of inertia) of the Terc-/- and Wrn-/-Terc-/- femurs compared to WT mice were also observed. Young Wrn-/-Terc-/- mice had a statistically significant increase in bone marrow fat content compared to young WT mice, which remained elevated in aged double mutants. Taken together, our results suggest that Terc-/- and Wrn-/-Terc-/- mutants recapitulate the human bone aging phenotype and are useful models for studying age-related osteoporosis.
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?
TAFs are associated with impaired osteoblast differentiation.
“with TAFs being associated with impaired osteoblast differentiation132,133”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [133]
The Introduction links telomere dysfunction in the mouse models to declines in osteoblast differentiation, and the Discussion reports dysfunctional osteoblast differentiation in those models. Neither passage identifies or measures telomere-associated foci (TAFs), so the specific association with TAFs is not established by this paper. (LLM, conf=0.82)
Experimental — accuracy not yet measuredLate-generation telomerase-deficient mice recapitulate features of osteoporosis including decreased bone volume, diminished osteoblast number and function, and increased porosity.
“late-generation telomerase-deficient mice recapitulate several features of osteoporosis, such as decreased bone volume, diminished osteoblast number and function, and increased porosity”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [133]
The Animals section identifies the Terc−/− mice as fourth-generation (G4). The Results and Discussion report decreased bone volume, increased cortical porosity, and impaired osteoblast function. But the Results say osteoblast number decreased with age across all genotypes, and the Discussion says numbers in aged mice were comparable across genotypes; the claimed decrease in osteoblast number relative to controls is not supported. (LLM, conf=0.92)
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
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650020617 · Cited by 5,015 · see citing works
Guidelines for assessment of bone microstructure in rodents using micro–computed tomography
Bouxsein, M., Boyd, S. K., Christiansen, B., Guldberg, R. E., Jepsen, K. J., & Müller, R. (2010) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.141 · Cited by 4,461 · see citing works
Bone Histomorphometry : Standardization of Nomenclature, Symbols, and Units
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · Cited by 3,258 · see citing works
PARFITT, A. M., Mathews, C. H. E., Villanueva, A. R., Kleerekoper, M., Frame, B., & Rao, D. S. (1983) · Journal of Clinical Investigation · doi:10.1172/jci111096 · Cited by 1,542 · see citing works
Mechanisms of Disease: is osteoporosis the obesity of bone?
Rosen, C. J., & Bouxsein, M. (2006) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0070 · Cited by 961 · see citing works
Zebaze, R., Ghasemzadeh, A., Bohte, A., Iuliano-Burns, S., Mirams, M., Price, R. I., Mackie, E. J., & Seeman, E. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60320-0 · Cited by 870 · see citing works
Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis
Justesen, J., Stenderup, K., Ebbesen, E., Mosekilde, L., Steiniche, T., & Kassem, M. (2004) · Biogerontology (Dordrecht) · doi:10.1023/a:1011513223894 · Cited by 847 · see citing works
EPSTKIN, C. J., MARTIN, G. M., SCHULTZ, A. L., & MOTULSKYS, A. G. (1966) · Medicine · doi:10.1097/00005792-196605000-00001 · Cited by 840 · see citing works
Kleerekoper, M., Villanueva, A. R., Stanciu, J., Rao, D. S., & PARFITT, A. M. (1985) · Calcified Tissue International · doi:10.1007/bf02554913 · Cited by 694 · see citing works
Defective Telomere Lagging Strand Synthesis in Cells Lacking WRN Helicase Activity
Crabbé, L., Verdún, R. E., Haggblom, C., & Karlseder, J. (2004) · Science · doi:10.1126/science.1103619 · Cited by 604 · see citing works
Essential role of limiting telomeres in the pathogenesis of Werner syndrome
Chang, S., Multani, A. S., Cabrera, N. G., Naylor, M. L., Laud, P., Lombard, D., Pathak, S., Guarente, L., & DePinho, R. A. (2004) · Nature Genetics · doi:10.1038/ng1389 · Cited by 462 · see citing works
PARFITT, A. M. (1984) · Calcified Tissue International · doi:10.1007/bf02406145 · Cited by 440 · see citing works
The Microanatomy of Trabecular Bone Loss in Normal Aging Men and Women
Aaron, J. E., Makins, N. B., & Sagreiya, K. (1987) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-198702000-00038 · Cited by 427 · see citing works
Telomere-binding Protein TRF2 Binds to and Stimulates the Werner and Bloom Syndrome Helicases
Opresko, P. L., von Kobbe, C., Lainé, J., Harrigan, J. A., Hickson, I. D., & Bohr, V. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205396200 · Cited by 389 · see citing works
Bone development and age-related bone loss in male C57BL/6J mice
Ferguson, V. L., Ayers, R. A., Bateman, T. A., & Simske, S. J. (2003) · Bone · doi:10.1016/s8756-3282(03)00199-6 · Cited by 379 · see citing works
MACDONALD, H. M., Nishiyama, K. K., Kang, J., Hanley, D. A., & Boyd, S. K. (2010) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.171 · Cited by 374 · 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
Age-related changes in osteogenic stem cells in mice
Bergman, R., Gazit, D., Kahn, A. J., Gruber, H. E., McDougall, S., & Hahn, T. J. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650110504 · Cited by 337 · see citing works
Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts
Wyllie, F. S., Jones, C. J., Skinner, J. W., Haughton, M. F., Wallis, C., Wynford-Thomas, D., Faragher, R. G. A., & Kipling, D. (2000) · Nature Genetics · doi:10.1038/71630 · Cited by 332 · see citing works
Senescence-accelerated mouse (SAM): a novel murine model of senescence
Takeda, T., Hosokawa, M., & Higuchi, K. (1997) · Experimental Gerontology · doi:10.1016/s0531-5565(96)00036-8 · Cited by 332 · see citing works
The Relevance of Mouse Models for Investigating Age-Related Bone Loss in Humans
Jilka, R. L. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt046 · Cited by 329 · see citing works
Nishiyama, K. K., MACDONALD, H. M., Buie, H. R., Hanley, D. A., & Boyd, S. K. (2009) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.091020 · Cited by 311 · see citing works
Age-Related Changes in Trabecular and Cortical Bone Microstructure
Chen, H., Zhou, X., Fujita, H., Onozuka, M., & Kubo, K. (2013) · International Journal of Endocrinology · doi:10.1155/2013/213234 · Cited by 307 · see citing works
Johnson, F. B., Marciniak, R. A., McVey, M., Stewart, S. A., Hahn, W. C., & Guarente, L. (2001) · The EMBO Journal · doi:10.1093/emboj/20.4.905 · Cited by 269 · see citing works
Self-citationBonyadi, M. J., Waldman, S. D., Liu, D., Aubin, J. E., Grynpas, M. D., & Stanford, W. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1036475100 · Cited by 247 · see citing works
Osteoblasts in osteoporosis: Past, emerging, and future anabolic targets
Marie, P. J., & Kassem, M. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0132 · Cited by 234 · see citing works
Matsushita, M., Tsuboyama, T., Kasai, R., Okumura, H., Yamamuro, T., Higuchi, K., Higuchi, K., Kohno, A., Yonezu, T., & Utani, A. (1986) · PubMed Central · Cited by 233 · see citing works
Ding, M. L., & Hvid, I. (2000) · Bone · doi:10.1016/s8756-3282(99)00281-1 · 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
Telomere Shortening Exposes Functions for the Mouse Werner and Bloom Syndrome Genes
Du, X., Shen, J., Kugan, N., Furth, E. E., Lombard, D. B., Cheung, C., Pak, S., Luo, G., Pignolo, R. J., DePinho, R. A., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.19.8437-8446.2004 · Cited by 213 · see citing works
Self-citationBell, K. L. D., Loveridge, N., Power, J., Garrahan, N. J., Stanton, M., Lunt, M., Meggitt, B. F., & REEVE, J. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.1.111 · Cited by 209 · see citing works
Kawaguchi, H., Manabe, N., Miyaura, C., Chikuda, H., Nakamura, K., & Kuro‐o, M. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5705 · Cited by 204 · see citing works
Distribution of Intracortical Porosity in Human Midfemoral Cortex by Age and Gender
Bousson, V., Meunier, A., Bergot, C., Vicaut, É., Rocha, M. A., Morais, M. H., Laval-Jeantet, A. M., & Larédo, J.-D. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.7.1308 · Cited by 200 · see citing works
Pathobiology of the senescence-accelerated mouse (SAM)
Takeda, T., Matsushita, T., Kurozumi, M., Takemura, K., Higuchi, K., & Hosokawa, M. (1997) · Experimental Gerontology · doi:10.1016/s0531-5565(96)00068-x · Cited by 191 · see citing works
Hematopoietic stem cell and progenitor defects in Sca-1/Ly-6A–null mice
Ito, C. Y., Li, C. Y. J., Bernstein, A., Dick, J. E., & Stanford, W. L. (2002) · Blood · doi:10.1182/blood-2002-06-1918 · Cited by 184 · see citing works
Sun, L.-Q., Lee, D. W., Zhang, Q., Xiao, W., Raabe, E. H., Meeker, A. K., Miao, D., Huso, D. L., & Arceci, R. J. (2004) · Genes & Development · doi:10.1101/gad.1176104 · Cited by 182 · see citing works
Expression of RANKL and OPG correlates with age-related bone loss in male C57BL/6 mice.
Cao, J., Venton, L., Sakata, T., & Halloran, B. P. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.2.270 · Cited by 173 · see citing works
Aging bone in men and women: beyond changes in bone mineral density
Russo, C. R., Lauretani, F., Bandinelli, S., Bartali, B., Iorio, A. D., Volpato, S., Guralnik, J. M., Harris, T. B., & Ferrucci, L. (2003) · Osteoporosis International · doi:10.1007/s00198-002-1322-y · Cited by 172 · see citing works
Mice deficient in Abl are osteoporotic and have defects in osteoblast maturation
Li, B., Boast, S., Santos, K. D. L., Schieren, I., Quiroz, M. E., Teitelbaum, S. L., Tondravi, M. M., & Goff, S. P. (2000) · Nature Genetics · doi:10.1038/73542 · Cited by 160 · see citing works
Mosekilde, L., Danielsen, C. C., & Gasser, J. A. (1994) · Endocrinology · doi:10.1210/endo.134.5.8156913 · Cited by 153 · see citing works
Effects of castration on the bone structure of male rats: A model of osteoporosis
Wink, C. S., & Felts, W. J. L. (1980) · Calcified Tissue International · doi:10.1007/bf02408524 · Cited by 151 · see citing works
Evaluation of the Pathogenesis of Skeletal Changes in Ovariectomized Rats*
Kalu, D. N., Hardin, R. R., & Cockerham, R. (1984) · Endocrinology · doi:10.1210/endo-115-2-507 · Cited by 151 · see citing works
The cancellous bone of the iliac crest
WAKAMATSU, E., & SISSONS, H. A. (1969) · Calcified Tissue International · doi:10.1007/bf02279116 · Cited by 142 · see citing works
Application of micro-ct assessment of 3-d bone microstructure in preclinical and clinical studies
Jiang, Y., Zhao, J., Liao, E.-Y., Dai, R.-C., Wu, X.-P., & Genant, H. K. (2005) · Journal of Bone and Mineral Metabolism · doi:10.1007/bf03026336 · Cited by 141 · see citing works
Defects in telomere maintenance molecules impair osteoblast differentiation and promote osteoporosis
Pignolo, R. J., Suda, R. K., McMillan, E. A., Shen, J., Lee, S., Choi, Y., Wright, A. C., & Johnson, F. B. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00350.x · Cited by 140 · see citing works
Self-citationAge related histomorphometric changes in bone in normal British men and women.
Rehman, M. T., Hoyland, J. A., Denton, J., & Freemont, A. J. (1994) · Journal of Clinical Pathology · doi:10.1136/jcp.47.6.529 · Cited by 130 · see citing works
Dyskeratosis Congenita - A Disease of Dysfunctional Telomere Maintenance
Mason, P., Wilson, D., & Bessler, M. (2005) · Current Molecular Medicine · doi:10.2174/1566524053586581 · Cited by 129 · cited 1× · see citing works
“…M ec ha ni sm s involved using mouse strains that had a low peak bone mass, including C57BL/6J, that would develop osteoporosis naturally with age (Matsushita et al., 1986; Perkins et al., 1994; Bergman et al., 1996; Takeda et al., 1997b; Takeda et al., 1997a; Takeda et al., 1997c; Cao et al.,…”
BackgroundAge‐related changes in cortical porosity of the midshaft of the human femur
Feik, S. A., Thomas, C. D. L., & Clement, J. G. (1997) · Journal of Anatomy · doi:10.1046/j.1469-7580.1997.19130407.x · Cited by 124 · see citing works
Raisz, L. G., & Rodan, G. A. (2003) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(02)00055-5 · Cited by 120 · see citing works
Impaired bone activity in aged rats: Alterations at the cellular and molecular levels
Liang, C. T., Barnes, J., Seedor, J. G., Quartuccio, H. A., Bolander, M. E., Jeffrey, J. J., & Rodan, G. A. (1992) · Bone · doi:10.1016/8756-3282(92)90087-d · Cited by 116 · see citing works
Effect of estrogens on bone marrow adipogenesis and Sirt1 in aging C57BL/6J mice
Elbaz, A., Rivas, D., & Duque, G. (2009) · Biogerontology (Dordrecht) · doi:10.1007/s10522-009-9221-7 · Cited by 111 · see citing works
Changes in quantitative bone histomorphometry in aging healthy men
Clarke, B. L., Ebeling, P. R., Jones, J. D., Wahner, H. W., O’Fallon, W. M., Riggs, B. L., & Fitzpatrick, L. A. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.6.8964862 · 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
Age-related changes in trabecular width and spacing in human iliac crest biopsies
Mellish, R. W. E., Garrahan, N. J., & Compston, J. (1989) · Bone and Mineral · doi:10.1016/0169-6009(89)90038-x · Cited by 103 · see citing works
Mullender, M. G., Tan, S., Vico, L., Alexandre, C., & Klein‐Nulend, J. (2005) · Calcified Tissue International · doi:10.1007/s00223-005-0043-6 · Cited by 101 · see citing works
Current advances in unraveling the function of the Werner syndrome protein
Ozgenc, A. I., & Loeb, L. A. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.03.020 · Cited by 98 · see citing works
Wang, H., Chen, Q., Lee, S., Choi, Y., Brad Johnson, F., & Pignolo, R. J. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00838.x · Cited by 81 · see citing works
Self-citationOverview of osteoporosis: pathophysiology and determinants of bone strength
Bono, C. M., & Einhorn, T. A. (2003) · European Spine Journal · doi:10.1007/s00586-003-0603-2 · Cited by 81 · see citing works
Birkenhäger-Frenkel, D. H., Courpron, P., Hüpscher, E. A., Clermonts, E., Coutinho, M., Schmitz, P. I. M., & Meunier, P. J. (1988) · PubMed · Cited by 80 · see citing works
Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation
Marie, P. J., & Kassem, M. S. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2113 · Cited by 76 · see citing works
Age-related bone loss in mice is associated with an increased osteoclast progenitor pool
Perkins, S. L., Gibbons, R., Kling, S. J., & Kahn, A. J. (1994) · Bone · doi:10.1016/8756-3282(94)90893-1 · Cited by 73 · see citing works
Shared Phenotypes Among Segmental Progeroid Syndromes Suggest Underlying Pathways of Aging
Höfer, A., Tran, R. T., Aziz, O. Z., Wright, W. E., Novelli, G., Shay, J. W., & Lewis, M. (2005) · The Journals of Gerontology Series A · doi:10.1093/gerona/60.1.10 · Cited by 70 · see citing works
Rasheed, N., Wang, X., Niu, Q., Yeh, J. K., & Li, B. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl116 · Cited by 67 · see citing works
Orchiectomy Increases Bone Marrow Interleukin-6 Levels in Mice
Zhang, J., Pugh, T. D., Stebler, B. S., Ershler, W. B., & Keller, E. T. (1998) · Calcified Tissue International · doi:10.1007/s002239900421 · Cited by 53 · see citing works
Ostertag, A., Cohen-Solal, M. E., Audran, M., Legrand, É., Marty, C., Chappard, D., & de Vernejoul, M. C. (2008) · Bone · doi:10.1016/j.bone.2008.11.004 · Cited by 47 · see citing works
Bone Histomorphometry in Male Idiopathic Osteoporosis
Pernow, Y., Hauge, E., Linder, K., Dahl, E., & Sääf, M. (2009) · Calcified Tissue International · doi:10.1007/s00223-009-9239-5 · Cited by 44 · see citing works
Abrogation of Cbl–PI3K Interaction Increases Bone Formation and Osteoblast Proliferation
Brennan, T. A., Adapala, N. S., Barbe, M. F., Yingling, V. R., & Sanjay, A. (2011) · Calcified Tissue International · doi:10.1007/s00223-011-9531-z · Cited by 40 · see citing works
Self-citationTakeda, T., Higuchi, K., & Hosokawa, M. (1997) · ILAR Journal · doi:10.1093/ilar.38.3.109 · Cited by 30 · see citing works
Singh, L., Brennan, T. A., Kim, J. H., Egan, K. P., McMillan, E. A., Chen, Q., Hankenson, K. D., Zhang, Y., Emerson, S. G., Johnson, F. B., et al. (2012) · Stem Cells · doi:10.1002/stem.1294 · Cited by 25 · see citing works
Self-citation
Flagged first, then by citations
1 of the 70 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Aging and aging-related diseases: from molecular mechanisms to interventions and treatments
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
Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443 · see citing works
Telomere dysfunction in ageing and age-related diseases
Rossiello, F., Jurk, D., Passos, J. F., & d’Adda di Fagagna, F. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00842-x · Cited by 754 · 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
Singh, L., Brennan, T. A., Russell, E., Kim, J., Chen, Q., Johnson, F. B., & Pignolo, R. J. (2016) · Bone · doi:10.1016/j.bone.2016.01.014 · Cited by 113 · see citing works
Self-citationPathology 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
The genetics of bone mass and susceptibility to bone diseases
Karasik, D., Rivadeneira, F., & Johnson, M. L. (2016) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2016.48 · Cited by 87 · see citing works
Induction of Accelerated Aging in a Mouse Model
Cai, N., Wu, Y., & Huang, Y. Y. (2022) · Cells · doi:10.3390/cells11091418 · Cited by 92 · see citing works
Tratwal, J., Labella, R., Bravenboer, N., Kerckhofs, G., Douni, E., Scheller, E., Badr, S., Karampinos, D., Beck-Cormier, S., Palmisano, B., et al. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00065 · Cited by 82 · see citing works
Concise Review: Musculoskeletal Stem Cells to Treat Age-Related Osteoporosis
Kiernan, J., Davies, J. E., & Stanford, W. L. (2017) · Stem Cells Translational Medicine · doi:10.1002/sctm.17-0054 · Cited by 74 · see citing works
Telomere function and regulation from mouse models to human ageing and disease
Jones-Weinert, C. W., Mainz, L., & Karlseder, J. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00800-5 · Cited by 57 · see citing works
Circadian disruption by shifting the light‐dark cycle negatively affects bone health in mice
Schilperoort, M., Bravenboer, N., Lim, J., Mletzko, K., Busse, B., van Ruijven, L. J., Kroon, J., Rensen, P. C. N., Kooijman, S., & Winter, E. M. (2019) · The FASEB Journal · doi:10.1096/fj.201901929r · Cited by 51 · see citing works
Chandra, A., Lagnado, A. B., Farr, J. N., Schleusner, M., Monroe, D. G., Saul, D., Passos, J. F., Khosla, S., & Pignolo, R. J. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4537 · Cited by 52 · see citing works
Self-citationGlucose tolerance female-specific QTL mapped in collaborative cross mice
Atamni, H. J. A., Ziner, Y., Mott, R., Wolf, L., & Iraqi, F. A. (2016) · Mammalian Genome · doi:10.1007/s00335-016-9667-2 · Cited by 43 · see citing works
Lei, P., Sun, R., Wang, L., Zhou, J., Wan, L., Zhou, T., & Hu, Y. (2015) · PLoS ONE · doi:10.1371/journal.pone.0146005 · Cited by 37 · 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
MiR-206 regulates the progression of osteoporosis via targeting HDAC4
Lu, Z., Wang, D., Wang, X., Zou, J., Sun, J., & Bi, Z. (2021) · European journal of medical research · doi:10.1186/s40001-021-00480-3 · Cited by 30 · see citing works
A cancer survivorship model for holistic cancer care and research
Sheikh-Wu, S. F., Anglade, D., & Downs, C. A. (2023) · Canadian Oncology Nursing Journal · doi:10.5737/236880763314 · Cited by 32 · see citing works
Pignolo, R. J. (2023) · Comprehensive physiology · doi:10.1002/j.2040-4603.2023.tb00253.x · Cited by 21 · see citing works
Self-citationPignolo, R. J. (2023) · Comprehensive physiology · doi:10.1002/cphy.c220012 · Cited by 42 · see citing works
Self-citationAddressing osteoblast senescence: Molecular pathways and the frontier of anti‐ageing treatments
Zhang, Z., Liu, P., Song, Y., Ma, L., Xu, Y., Lei, J., Tong, B., Zhu, D., Liang, H., Wang, H., et al. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70417 · Cited by 18 · see citing works
Telomere length as a predictive biomarker in osteoporosis (Review)
Kakridonis, F., Pneumatikos, S. G., Vakonaki, E., Berdiaki, A., Tzatzarakis, M. N., Fragkiadaki, P., Spandidos, D. A., Baliou, S., Ιωάννου, Π., Hatzidaki, E., et al. (2023) · Biomedical Reports · doi:10.3892/br.2023.1669 · Cited by 15 · see citing works
Presbítero-Espinosa, G., Gutiérrez, D., Lemus-Martínez, W. R., Vílchez‐Cavazos, F., García, P., & Arizmendi-Morquecho, A. M. (2021) · Applied Sciences · doi:10.3390/app11125479 · Cited by 13 · see citing works
Mouse models in modeling aging and cancer
Li, H., Wei, C., Zhou, R., Wang, B., Zhang, Y., Shao, C., & Luo, Y. (2019) · Experimental Gerontology · doi:10.1016/j.exger.2019.03.002 · Cited by 11 · 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
Single-cell multi-omics identify novel regulators required for osteoclastogenesis during aging
Li, H., Xu, W., Tan, J.-C., Hong, Y.-M., He, J., Zhao, B.-P., Zhou, J., Zheng, Y.-M., Lei, M., Zheng, X., et al. (2024) · iScience · doi:10.1016/j.isci.2024.110734 · Cited by 10 · see citing works
Wu, J., Zhang, L., Zhao, Z., Liu, Y., Li, Z., Feng, X., Zhang, L., Yao, X., Du, J. C., Chen, L., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102783 · Cited by 10 · see citing works
Pignolo, R. J., & Chandra, A. (2025) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2025.112025 · Cited by 10 · see citing works
Self-citationAdvances in biomarkers and diagnostic significance of organ aging
Chen, Y., Li, J., Liu, X., Geng, Z., Xu, K., & Su, J. (2023) · Fundamental Research · doi:10.1016/j.fmre.2023.03.009 · Cited by 8 · see citing works
Contributions of Telomere Biology to Human Age-Related Disease
Yang, T.-L., Song, S., & Johnson, F. B. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-411596-5.00007-1 · Cited by 8 · see citing works
Self-citationChandra, A., Rosenzweig, A. B., & Pignolo, R. J. (2018) · Springer eBooks · doi:10.1007/978-3-319-72228-3_1 · Cited by 6 · see citing works
Self-citationTargeting G-quadruplex for rescuing impaired chondrogenesis in WRN-deficient stem cells
Leung, A. O.-W., Yiu, T.-C., Liu, L., Tam, H.-Y., Gu, S., Tu, J., Pei, D., & Cheung, H. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00939-8 · Cited by 5 · see citing works
Almeida, M., & Manolagas, S. C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814841-9.00012-9 · Cited by 4 · see citing works
Gimble, J. M., Floyd, Z. E., Kassem, M. S., & NUTTALL, M. E. (2016) · Springer eBooks · doi:10.1007/978-3-319-25976-5_2 · Cited by 4 · see citing works
Verlinden, L., Li, S., Veldurthy, V., Carmeliet, G., & Christakos, S. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1310466 · Cited by 3 · see citing works
Skeletal 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
miR-370-3p affects the progression of postmenopausal osteoporosis through targeting INO80
Yang, Z., Sheng, Y., Liu, X., Cen, M., & Xu, Y. J. (2025) · Hereditas · doi:10.1186/s41065-025-00502-8 · Cited by 2 · see citing works
Ng, G. Y. Q., & Hande, M. P. (2024) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2024.503773 · Cited by 2 · see citing works
Impact of senescence on bone quality: lessons from animal models of aging
Richards, P. J. (2014) · Drug Discovery Today Disease Models · doi:10.1016/j.ddmod.2014.11.001 · Cited by 1 · see citing works
Modèle de survie au cancer appliqué aux soins holistiques et à la recherche
Sheikh-Wu, S. F., Anglade, D., & Downs, C. A. (2023) · Canadian Oncology Nursing Journal · doi:10.5737/2368807633117 · Cited by 1 · see citing works
Telomeres Shortening: A Mere Replicometer?
Victorelli, S. G., & Passos, J. F. (2016) · Healthy ageing and longevity · doi:10.1007/978-3-319-26239-0_7 · Cited by 1 · see citing works
Helicases and Their Relevance to Aging
Crouch, J. D., Banerjee, T., Awate, S., Bharti, S. K., & Brosh, R. M. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00072-5
The role of melanocyte senescence in skin ageing
Victorelli, S. G. (2018)
Coppedè, F. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00002-6
Farr, J. N., & Chandra, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15500-0.00017-7
- Authors
- Brennan, T. A., Egan, K. P., Lindborg, C. M., Chen, Q., Sweetwyne, M. T., Hankenson, K. D., Xie, S. X., Johnson, F. B., & Pignolo, R. J.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Pignolo, Robert J.
- ORCID
- Venue
- Disease Models & Mechanisms
- Publisher
- The Company of Biologists
- Published
- 2014-01-01
- Volume
- 7
- Issue
- 5
- Pages
- 583-92
- ISSN
- 1754-8403 (ISSN-L)
- 1754-8411
- PMC
- PMC4007409
- OpenAlex
- W2119337287
- Cited by
- 45
- References
- 70
- Citations by year
- 2025: 4 · 2024: 6 · 2023: 7 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 1 · 2016: 6 · 2015: 2 · 2014: 1
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Disease Models & Mechanisms (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- HighWire Press Open Archive (submittedVersion)
- Funders
- University of Pennsylvania
- Perelman School of Medicine, University of Pennsylvania
- National Institute on Aging (R01AG028873)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR050950)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- 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
- Keywords
- telomere dysfunction, senile osteoporosis, bone aging, Werner syndrome, dyskeratosis congenita, telomerase, cellular senescence, trabecular bone microarchitecture, cortical bone thinning, osteoblast dysfunction, bone formation rate, bone marrow fat, bone mechanical properties, progeroid disorder, mouse model
- MeSH terms
- Werner Syndrome Helicase, Animals, Bone and Bones, Bone Marrow, Bone Resorption, Cell Count, Disease Models, Animal, Humans, Kinetics, Mutation, Osteoblasts, Osteoclasts, Osteogenesis, Osteoporosis, Phenotype, Telomere, Telomerase, Adiposity, Mice, RecQ Helicases
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
