TGFβ-induced degradation of TRAF3 in mesenchymal progenitor cells causes age-related osteoporosis
Open accessAbstract
Inflammaging induces osteoporosis by promoting bone destruction and inhibiting bone formation. TRAF3 limits bone destruction by inhibiting RANKL-induced NF-κB signaling in osteoclast precursors. However, the role of TRAF3 in mesenchymal progenitor cells (MPCs) is unknown. Mice with TRAF3 deleted in MPCs develop early onset osteoporosis due to reduced bone formation and enhanced bone destruction. In young mice TRAF3 prevents β-catenin degradation in MPCs and maintains osteoblast formation. However, TRAF3 protein levels decrease in murine and human bone samples during aging when TGFβ1 is released from resorbing bone. TGFβ1 induces degradation of TRAF3 in murine MPCs and inhibits osteoblast formation through GSK-3β-mediated degradation of β-catenin. Thus, TRAF3 positively regulates MPC differentiation into osteoblasts. TRAF3 deletion in MPCs activated NF-κB RelA and RelB to promote RANKL expression and enhance bone destruction. We conclude that pharmacologic stabilization of TRAF3 during aging could treat/prevent age-related osteoporosis by inhibiting bone destruction and promoting bone formation.
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Bone samples from aged mice and humans have high levels of TGF-β and can stimulate breakdown of TRAF3 to inhibit differentiation of mesenchymal progenitor cells into osteoblasts.
“bone samples from aged mice and humans have high levels of TGF-β and can stimulate the breakdown of TNF receptor-associated factor 3 to inhibit the differentiation of mesenchymal progenitor cells into osteoblasts [94].”
From Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature (2024) · cites this paper as [94]
In the absence of TRAF3 expression, Nf-κB noncanonical signaling is activated with an increase in RANKL production and is associated with osteoclastogenesis.
“In the absence of TRAF3 expression, Nf-κB noncanonical signaling is activated with an increase in RANKL production and therefore is associated with osteoclastogenesis.207”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [207]
TGF-β1 favors RANKL production in osteoblast precursors by inducing TRAF3 degradation.
“Moreover, TGF-β1 favors RANKL production in osteoblast precursors by inducing TRAF3 degradation.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [207]
Expression of TRAF3 in osteoblast precursors favors stabilization of β-catenin and their differentiation into mature osteoblasts.
“The expression of TRAF3, which is an inhibitor of noncanonical Nf-κB signaling, in osteoblast precursors favors the stabilization of β-catenin and, therefore, their differentiation into mature osteoblasts.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [207]
TRAF3 expression reduces with age.
“TRAF3 has been shown to reduce expression with age [82].”
From Early onset senescence and cognitive impairment in a murine model of repeated mTBI (2021) · cites this paper as [82]
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Cites
Massagué, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3434 · Cited by 3,130 · see citing works
Functions of RANKL/RANK/OPG in bone modeling and remodeling
Boyce, B. F., & Xing, L. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.03.018 · Cited by 1,844 · see citing works
Self-citationEmbryonic 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
Men and mice: Relating their ages
Dutta, S., & Sengupta, P. (2016) · Life Sciences · doi:10.1016/j.lfs.2015.10.025 · Cited by 1,710 · see citing works
Day, T. F., Guo, X., Garrett-Beal, L., & Yang, Y. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.03.016 · Cited by 1,616 · see citing works
The glamour and gloom of glycogen synthase kinase-3
Jope, R. S., & Johnson, G. V. W. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2003.12.004 · Cited by 1,522 · see citing works
Matrix-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
TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signalingPreprint
Lomaga, M. A., Yeh, W., Sarosi, I., Duncan, G. S., Furlonger, C. L., Ho, A. P., Morony, S., Capparelli, C., Van, G. Y., Kaufman, S., et al. (1999) · Genes & Development · doi:10.1101/gad.13.8.1015 · Cited by 1,253 · see citing works
TGF-β1–induced migration of bone mesenchymal stem cells couples bone resorption with formation
Tang, Y., Wu, X., Lei, W., Pang, L., Wan, C., Shi, Z., Zhao, L., Nagy, T. R., Peng, X., Hu, J., et al. (2009) · Nature Medicine · doi:10.1038/nm.1979 · Cited by 1,165 · see citing works
Canonical Wnt/β-Catenin Signaling Prevents Osteoblasts from Differentiating into Chondrocytes
Hill, T. P., Später, D., Taketo, M. M., Birchmeier, W., & Hartmann, C. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.02.013 · Cited by 1,086 · see citing works
Estrogen deficiency and bone loss: an inflammatory tale
Weitzmann, M. N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28550 · Cited by 990 · see citing works
Promiscuous Mutations Activate the Noncanonical NF-κB Pathway in Multiple Myeloma
Keats, J. J., Fonseca, R., Chesi, M., Schop, R., Baker, A., Chng, W.-J., Van Wier, S., Tiedemann, R., Shi, C.-X., Sebag, M., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.07.003 · Cited by 983 · see citing works
Pathogenesis of bone fragility in women and men
Seeman, E. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08706-8 · Cited by 909 · see citing works
GSK3: a multifaceted kinase in Wnt signaling
Wu, D., & Pan, W. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.10.002 · Cited by 862 · see citing works
Naito, A., Azuma, S., Tanaka, S., Miyazaki, T., Takaki, S., Takatsu, K., Nakao, K., Nakamura, K., Katsuki, M., Yamamoto, T. S., et al. (1999) · Genes to Cells · doi:10.1046/j.1365-2443.1999.00265.x · Cited by 626 · see citing works
Zarnegar, B. J., Wang, Y., Mahoney, D. J., Dempsey, P. W., Cheung, H. H., He, J., Shiba, T. L., Yang, X., Yeh, W., Mak, T. W., et al. (2008) · Nature Immunology · doi:10.1038/ni.1676 · Cited by 607 · see citing works
Vallabhapurapu, S., Matsuzawa, A., Zhang, W., Tseng, P., Keats, J. J., Wang, H., Vignali, D. A. A., Bergsagel, P. L., & Karin, M. (2008) · Nature Immunology · doi:10.1038/ni.1678 · Cited by 605 · see citing works
Aging and bone loss: new insights for the clinician
Demontiero, O., Vidal, C., & Duque, G. (2011) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x11430858 · Cited by 565 · see citing works
Nakashima, T., Kobayashi, Y., Yamasaki, S., Kawakami, A., Eguchi, K., Sasaki, H., & Sakai, H. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3379 · Cited by 508 · see citing works
Inhibition 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
Baud, V., Liu, Z.-G., Bennett, B. L., Suzuki, N., Xia, Y., & Karin, M. (1999) · Genes & Development · doi:10.1101/gad.13.10.1297 · Cited by 464 · see citing works
Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis
Langdahl, B. L., Ferrari, S., & Dempster, D. W. (2016) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x16670154 · Cited by 439 · see citing works
Dimorphic effects of Notch signaling in bone homeostasis
Engin, F., Yao, Z., Yang, T., Zhou, G. D., Bertin, T., Jiang, M. M., Chen, Y., Wang, L. E., Zheng, H., Sutton, R. E., et al. (2008) · Nature Medicine · doi:10.1038/nm1712 · Cited by 413 · see citing works
Self-citationUdagawa, N., Takahashi, N., Jimi, E., Matsuzaki, K., Tsurukai, T., Itoh, K., Nakagawa, N., Yasuda, H., Goto, M., Tsuda, E., et al. (1999) · Bone · doi:10.1016/s8756-3282(99)00210-0 · Cited by 410 · 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
Martin, J. F., Bradley, A., & Olson, E. N. (1995) · Genes & Development · doi:10.1101/gad.9.10.1237 · Cited by 351 · see citing works
NF-κB-Mediated Regulation of Osteoclastogenesis
Boyce, B. F., Xiu, Y., Li, J., Xing, L., & Yao, Z. (2015) · Endocrinology and Metabolism · doi:10.3803/enm.2015.30.1.35 · Cited by 316 · see citing works
Self-citationImmunology of Osteoporosis: A Mini-Review
Pietschmann, P., Mechtcheriakova, D., Meshcheryakova, A., Föger‐Samwald, U., & Ellinger, I. (2015) · Gerontology · doi:10.1159/000431091 · Cited by 289 · see citing works
Cai, Q., Sun, H., Peng, Y., Lü, J., Nikolovska‐Coleska, Z., McEachern, D., Liu, L., Qiu, S., Yang, C., Miller, R. S., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm101505d · Cited by 274 · see citing works
Prx1 and Prx2 in skeletogenesis: roles in the craniofacial region, inner ear and limbs
ten Berge, D., Brouwer, A., Korving, J., Martin, J. F., & Meijlink, F. C. P. W. (1998) · Development · doi:10.1242/dev.125.19.3831 · Cited by 274 · see citing works
Age-Related Bone Loss: Old Bone, New Facts
Chan, G. K., & Duque, G. (2002) · Gerontology · doi:10.1159/000048929 · Cited by 259 · see citing works
Matsushita, T., Chan, Y. Y., Kawanami, A., Balmes, G. C., Landreth, G. E., & Murakami, S. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01549-08 · Cited by 232 · see citing works
Kim, S., Yamazaki, M., Zella, L. A., Shevde, N. K., & Pike, J. W. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00353-06 · Cited by 223 · see citing works
Pathogenesis of Age-Related Bone Loss in Humans
Khosla, S. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/gls163 · Cited by 222 · see citing works
Li, P., Schwarz, E. M., O'Keefe, R. J., Ma, L., Boyce, B. F., & Xing, L. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.0301233 · Cited by 220 · see citing works
Self-citationXie, P., Stunz, L. L., Larison, K. D., Yang, B., & Bishop, G. A. (2007) · Immunity · doi:10.1016/j.immuni.2007.07.012 · Cited by 217 · see citing works
TRAF6 ubiquitinates TGFβ type I receptor to promote its cleavage and nuclear translocation in cancer
Mu, Y., Sundar, R., Thakur, N., Ekman, M., Gudey, S. K., Yakymovych, M., Hermansson, A., Dimitriou, H., Bengoechea-Alonso, M. T., Ericsson, J., et al. (2011) · Nature Communications · doi:10.1038/ncomms1332 · Cited by 182 · see citing works
Meednu, N., Zhang, H., Owen, T., Sun, W. S., Wang, V., Cistrone, C., Rangel‐Moreno, J., Xing, L., & Anolik, J. H. (2015) · Arthritis & Rheumatology · doi:10.1002/art.39489 · Cited by 182 · see citing works
Self-citationBorton, A. J., Frederick, J. P., Datto, M., Wang, X.-F., & Weinstein, R. S. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.10.1754 · Cited by 179 · see citing works
Dole, N. S., Mazur, C. M., Acevedo, C., Lopez, J. P., Monteiro, D. A., Fowler, T. W., Gludovatz, B., Walsh, F., Regan, J. N., Messina, S., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.115 · Cited by 173 · see citing works
Seo, H., & Serra, R. A. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2007.07.040 · Cited by 167 · see citing works
Fu, Q., Manolagas, S., & O'Brien, C. A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00356-06 · Cited by 165 · see citing works
Chloroquine reduces osteoclastogenesis in murine osteoporosis by preventing TRAF3 degradation
Xiu, Y., Xu, H., Zhao, C., Li, J., Morita, Y., Yao, Z., Xing, L., & Boyce, B. F. (2014) · Journal of Clinical Investigation · doi:10.1172/jci66947 · Cited by 164 · see citing works
Self-citationAge-Related Changes in Bone Turnover in Men
Fatayerji, D., & Eastell, R. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.7.1203 · Cited by 163 · see citing works
NF-kappaB p100 limits TNF-induced bone resorption in mice by a TRAF3-dependent mechanism.
Yao, Z., Xing, L., & Boyce, B. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38716 · Cited by 160 · see citing works
Self-citationRegulation of NF-κB signalling by the mono-ADP-ribosyltransferase ARTD10
Verheugd, P., Forst, A. H., Milke, L., Herzog, N., Feijs, K. L. H., Kremmer, E., Kleine, H. O., & Lüscher, B. (2013) · Nature Communications · doi:10.1038/ncomms2672 · Cited by 160 · see citing works
Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes
Molony, R. D., Nguyen, J. T., Kong, Y., Montgomery, R. R., Shaw, A. C., & Iwasaki, A. (2017) · Science Signaling · doi:10.1126/scisignal.aan2392 · Cited by 154 · see citing works
TGF-β Inhibition Restores Terminal Osteoblast Differentiation to Suppress Myeloma Growth
Takeuchi, K., Abe, M., Hiasa, M., Oda, A., Amou, H., Kido, S., Harada, T., Tanaka, O., Miki, H., Nakamura, S., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009870 · Cited by 138 · see citing works
Osteoporosis: The Result of an ‘Aged’ Bone Microenvironment
Yu, B., & Wang, C. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.06.002 · Cited by 138 · see citing works
The relationship between osteoarthritis and osteoporosis
Im, G., & Kim, M. (2013) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-013-0531-0 · Cited by 117 · see citing works
Yasui, T., Kadono, Y., Nakamura, M., Oshima, Y., Matsumoto, T., Masuda, H., Hirose, J., Omata, Y., Yasuda, H., Imamura, T., et al. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.357 · Cited by 114 · see citing works
Smad4 is required for maintaining normal murine postnatal bone homeostasis
Tan, X., Weng, T., Zhang, J., Jian, W., Li, W., Wan, H., Lan, Y., Cheng, X., Hou, N., Liu, H., et al. (2007) · Journal of Cell Science · doi:10.1242/jcs.03466 · Cited by 106 · see citing works
TRAF3 Controls Activation of the Canonical and Alternative NFκB by the Lymphotoxin Beta Receptor
Bista, P., Zeng, W., Ryan, S. T., Bailly, V., Browning, J. L., & Lukashev, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.076091 · Cited by 76 · see citing works
Yao, Z., Lei, W., Duan, R., Li, Y., Luo, L., & Boyce, B. F. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.771816 · Cited by 75 · see citing works
Self-citationShrier, I. (2004) · British Journal of Sports Medicine · doi:10.1136/bjsm.2003.011262 · Cited by 73 · see citing works
NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation
Yao, Z., Li, Y.-Y., Yin, X., Dong, Y., Xing, L., & Boyce, B. F. (2014) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2108 · Cited by 72 · see citing works
Self-citationLian, N., Lin, T., Liu, W., Wang, W., Li, L., Sun, S. W., Nyman, J. S., & Yang, X. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.372458 · Cited by 62 · see citing works
Zhao, Z., Hou, X., Yin, X., Li, Y., Duan, R., Boyce, B. F., & Yao, Z. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135728 · Cited by 58 · see citing works
Self-citationOsteoprotegerin, the bone protector, is a surprising target for β-catenin signaling
Boyce, B. F., Xing, L., & Chen, D. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.11.011 · Cited by 54 · see citing works
Self-citationNagel, I., Bug, S., Tönnies, H., Ammerpohl, O., Richter, J., Vater, I., Callet‐Bauchu, E., Calasanz, M. J., Martinez-Climent, J. A., Bastard, C., et al. (2009) · Leukemia · doi:10.1038/leu.2009.149 · Cited by 53 · see citing works
Kirby, L. A., Schott, J. T., Noble, B. L., Mendez, D. C., Caseley, P. S., Peterson, S. C., Routledge, T. J., & Patel, N. V. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039329 · Cited by 49 · see citing works
Bishop, K. A., Coy, H. M., Nerenz, R. D., Meyer, M. B., & Pike, J. W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.231548 · Cited by 44 · see citing works
Salazar, V. S., Zarkadis, N. J., Huang, L. P., Norris, J. Y., Grimston, S. K., Mbalaviele, G., & Civitelli, R. (2013) · Journal of Cell Science · doi:10.1242/jcs.131953 · Cited by 43 · see citing works
Malignant Autosomal Recessive Osteopetrosis Caused by Spontaneous Mutation of Murine <i>Rank</i>
Kapur, R. P., Yao, Z., Iida, M. H., Clarke, C. M., Doggett, B., Xing, L., & Boyce, B. F. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040713 · Cited by 39 · see citing works
Self-citationTalley-Ronsholdt, D. J., Lajiness, E. J., & Nagodawithana, K. (1995) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/bf02634001 · Cited by 39 · see citing works
Autophagy acts through TRAF3 and RELB to regulate gene expression via antagonism of SMAD proteins
Newman, A. C., Kemp, A. J., Drabsch, Y., Behrends, C., & Wilkinson, S. (2017) · Nature Communications · doi:10.1038/s41467-017-00859-z · Cited by 38 · see citing works
Onal, M., John, H. C. S., Danielson, A. L., & Pike, J. W. (2015) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2698 · Cited by 37 · see citing works
TRAF3 as a powerful and multitalented regulator of lymphocyte functions
Bishop, G. A. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.2mr0216-063r · Cited by 32 · see citing works
TRAF3: a novel tumor suppressor gene in macrophages
Lalani, A., Luo, C., Han, Y., & Xie, P. (2015) · Macrophage · doi:10.14800/macrophage.1009 · Cited by 29 · see citing works
Salazar, V. S., Zarkadis, N. J., Huang, L. P., Watkins, M. P., Kading, J. C., Bonar, S. L., Norris, J. Y., Mbalaviele, G., & Civitelli, R. (2013) · Journal of Cell Science · doi:10.1242/jcs.132233 · Cited by 27 · see citing works
Flagged first, then by citations
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Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482 · see citing works
Regulation of TNF-Induced Osteoclast Differentiation
Yao, Z., Getting, S. J., & Locke, I. C. (2021) · Cells · doi:10.3390/cells11010132 · Cited by 280 · see citing works
“TRAF3 also inhibits OC formation indirectly by limiting NF-κB mediated RANKL production by MPCs [94].”
BackgroundInfluentialSelf-citationThe diverse roles of neutrophils from protection to pathogenesis
Herro, R., & Grimes, H. L. (2024) · Nature Immunology · doi:10.1038/s41590-024-02006-5 · Cited by 149 · see citing works
Zhou, Y., Deng, Y., Liu, Z., Yin, M., Hou, M., Zhao, Z., Zhou, X., & Yin, L. (2021) · Science Advances · doi:10.1126/sciadv.abl6432 · Cited by 126 · see citing works
Wang, Y., Shen, S., Hu, T., Williams, G. R., Bian, Y., Feng, B., Liang, R., & Weng, X. (2021) · ACS Nano · doi:10.1021/acsnano.1c00461 · Cited by 113 · see citing works
Age-associated callus senescent cells produce TGF-β1 that inhibits fracture healing in aged mice
Liu, J., Zhang, J., Lin, X., Boyce, B. F., Zhang, H., & Xing, L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci148073 · Cited by 112 · see citing works
Self-citationRegulation of bone homeostasis: signaling pathways and therapeutic targets
Wu, Z., Li, W., Jiang, K., Lin, Z., Qian, C., Wu, M., Xia, Y., Li, N., Zhang, H., Xiao, H.-X., et al. (2024) · MedComm · doi:10.1002/mco2.657 · Cited by 115 · see citing works
Liu, H., Yi, X., Tu, S., Cheng, C., & Luo, J. F. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.111074 · Cited by 90 · see citing works
Searching for the link between inflammaging and sarcopenia
Wang, T. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101611 · Cited by 88 · see citing works
Nuclear Factor-Kappa B Regulation of Osteoclastogenesis and Osteoblastogenesis
Boyce, B. F., Li, J., Yao, Z., & Xing, L. (2023) · Endocrinology and Metabolism · doi:10.3803/enm.2023.501 · Cited by 82 · see citing works
Self-citationDai, Q.-D., Ma, Y., Xu, Z., Zhang, L., Yang, H., Liu, Q., & Wang, J.-Z. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118626 · Cited by 74 · see citing works
TNF Receptor-Associated Factor 6 Mediates TNFα-Induced Skeletal Muscle Atrophy in Mice During Aging
Li, J., Yi, X., Yao, Z., Chakkalakal, J. V., Xing, L., & Boyce, B. F. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4021 · Cited by 74 · see citing works
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Martinis, M. D., Sirufo, M. M., Suppa, M., & Ginaldi, L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041239 · Cited by 68 · see citing works
Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging
Wang, H., Yuan, T., Wang, Y., Liu, C., Li, D., Li, Z., & Sun, S. (2024) · Aging Cell · doi:10.1111/acel.14092 · Cited by 60 · see citing works
Enhanced osteogenesis and therapy of osteoporosis using simvastatin loaded hybrid system
Wu, T., Sun, J., Tan, L., Yan, Q., Li, L., Chen, L., Liu, X., & Bin, S. (2020) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.03.004 · Cited by 54 · see citing works
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Lin, M., Ji, X., Lv, Y., Cui, D., & Xie, J. (2023) · Disease Markers · doi:10.1155/2023/7787803 · Cited by 52 · see citing works
The immunological significance of tumor necrosis factor receptor-associated factors (TRAFs)
So, T. (2021) · International Immunology · doi:10.1093/intimm/dxab058 · Cited by 51 · see citing works
Huang, X., Lan, Y., Shen, J., Chen, Z., & Xie, Z. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.69816 · Cited by 48 · see citing works
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Targeting anti-cancer agents to bone using bisphosphonates
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Wang, T., Zhou, D., & Hong, Z. (2025) · MedComm · doi:10.1002/mco2.70030 · Cited by 46 · see citing works
Li, J., Yao, Z., Liu, X. Z., Duan, R., Yi, X., Ayoub, A., Sanders, J. O., Mesfin, A., Xing, L., & Boyce, B. F. (2023) · Nature Communications · doi:10.1038/s41467-023-35801-z · Cited by 46 · see citing works
Self-citationYe, C., Hou, W., Chen, M., Lu, J., Chen, E., Tang, L. F., Hang, K., Ding, Q., Li, Y., Zhang, W., et al. (2019) · Cell Proliferation · doi:10.1111/cpr.12752 · Cited by 44 · see citing works
Early onset senescence and cognitive impairment in a murine model of repeated mTBI
Schwab, N., Ju, Y., & Hazrati, L.-N. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01190-x · Cited by 39 · see citing works
GAS5 protects against osteoporosis by targeting UPF1/SMAD7 axis in osteoblast differentiation
Li, M., Xie, Z., Li, J., Lin, J., Guan, Z., Liu, W., Tang, S., Cen, S., Ye, G., Li, Z., et al. (2020) · eLife · doi:10.7554/elife.59079 · Cited by 39 · see citing works
Self-citationGao, Y., Zou, Y., Sokolowskei, D., Xing, X., Tower, R. J., Lai, Z., Shi, J., Zhu, L., Zheng, Q., James, A. W., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.02.034 · Cited by 36 · see citing works
Zeng, C., Wang, S., Chen, F., Wang, Z., Li, J., Xie, Z., Ma, M., Wang, P., Shen, H., & Wu, Y. (2022) · Phytotherapy Research · doi:10.1002/ptr.7610 · Cited by 35 · see citing works
Self-citationZhao, S., Qiao, Z., Pfeifer, R., Pape, H.-C., Mao, K., Tang, H., Meng, B., Chen, S., & Liu, H. (2024) · European Journal of Medical Research · doi:10.1186/s40001-023-01604-7 · Cited by 35 · see citing works
Terpenoid treatment in osteoporosis: this is where we have come in research
Bellavia, D., Caradonna, F., Dimarco, E., Costa, V., Carina, V., Luca, A. D., Raimondi, L., Gentile, C., Alessandro, R., Fini, M., et al. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.07.011 · Cited by 32 · see citing works
Exercise and osteoimmunology in bone remodeling
Zhao, Z., Du, Y., Yan, K., Zhang, L., & Guo, Q. (2024) · The FASEB Journal · doi:10.1096/fj.202301508rrr · Cited by 33 · see citing works
Hu, Z., Tang, Q., Yan, D., Zheng, G., Gu, M., Luo, Z., Mao, C., Qian, Z., Ni, W., & Shen, L. (2020) · Applied Materials Today · doi:10.1016/j.apmt.2020.100906 · Cited by 30 · see citing works
Xia, H., Liu, J., Yang, W., Liu, M., Luo, Y., Yang, Z., Xie, J., Zeng, H., Xu, R., Ling, H., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.654714 · Cited by 30 · see citing works
Li, M., Li, H., Li, L., Liu, L., Chen, G., Jiang, W., Xu, W., Zhu, C., Yao, G., & Fang, S. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01023 · Cited by 29 · see citing works
Li, Z., Xue, H., Tan, G., & Xu, Z. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.12428 · Cited by 29 · see citing works
Han, X., Ren, J., Lohner, H., Yakoumatos, L., Liang, R., & Wang, H. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102036 · Cited by 28 · see citing works
Saedi, A. A., Stupka, N., & Duque, G. (2020) · Handbook of experimental pharmacology · doi:10.1007/164_2020_358 · Cited by 26 · see citing works
The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases
Tudorancea, I. M., Ciorpac, M., Stanciu, G. D., Caratașu, C.-C., Săcărescu, A., Ignat, B. E., Burlui, A., Rezuş, E., Creangă-Murariu, I., Alexa‐Stratulat, T., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10102492 · Cited by 26 · see citing works
Yi, X., Liu, X., Kenney, H. M., Duan, R., Lin, X., Schwarz, E. M., & Yao, Z. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4447 · Cited by 23 · see citing works
Self-citationHuang, C., Zheng, Y., Bai, J., Shi, C., Shi, X., Shan, H., & Zhou, X. (2020) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2020.10.011 · Cited by 25 · see citing works
Patel, D., & Saxena, B. (2024) · Journal of Orthopaedic Reports · doi:10.1016/j.jorep.2024.100472 · Cited by 23 · see citing works
Yao, Z., Ayoub, A., Srinivasan, V., Wu, J., Tang, C., Duan, R., Milosavljevic, A., Xing, L., Ebetino, F. H., Frontier, A. J., et al. (2024) · Bone Research · doi:10.1038/s41413-024-00352-6 · Cited by 21 · see citing works
Self-citationLei, W., Duan, R., Li, J., Liu, X. Z., Huston, A. J., Boyce, B. F., & Yao, Z. (2020) · Scientific Reports · doi:10.1038/s41598-020-64018-z · Cited by 20 · see citing works
Self-citationWang, J., Xin, Y., Dong, Z., Li, S., & Yang, G. (2025) · Experimental Gerontology · doi:10.1016/j.exger.2025.112974 · Cited by 21 · see citing works
Yang, Y., Yang, M., Shi, D., Chen, K., Zhao, J., He, S., Bai, Y., Shen, P., & Ni, H. (2021) · JOR Spine · doi:10.1002/jsp2.1184 · Cited by 19 · see citing works
Wang, D., Cai, G., Wang, H., & He, J. (2020) · Stem Cells and Development · doi:10.1089/scd.2019.0276 · Cited by 19 · see citing works
Endothelial BMAL1 decline during aging leads to bone loss by destabilizing extracellular fibrillin-1
Yin, Y., Tang, Q., Yang, J., Gui, S., Zhang, Y., Shen, Y., Zhou, X., Yu, S., Chen, G., Sun, J., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci176660 · Cited by 17 · see citing works
Advances in the Study of the Mechanisms of Physiological Root Resorption in Deciduous Teeth
Xiao, M., Qian, H., Lv, J., & Peixuan, W. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2022.850826 · Cited by 17 · see citing works
CUL4B orchestrates mesenchymal stem cell commitment by epigenetically repressing KLF4 and C/EBPδ
Yu, R., Han, H. J., Chu, S., Ding, Y., Jin, S., Wang, Y., Jiang, W., Liu, Y., Zou, Y., Wang, Μ., et al. (2023) · Bone Research · doi:10.1038/s41413-023-00263-y · Cited by 15 · see citing works
Tu, M., Han, K.-Y., Lan, Y., Chang, K., Lai, C., Staniczek, T., Lai, C., Chong, K., & Chen, C. (2021) · Genes · doi:10.3390/genes12060930 · Cited by 15 · see citing works
Zhang, H., Ge, G., Zhang, W., Sun, H., Liang, X., Xia, Y., Du, J., Wu, Z., Bai, J., Yang, H., et al. (2024) · Advanced Science · doi:10.1002/advs.202404080 · Cited by 13 · see citing works
Shang, Q., Zhao, W., Shen, G., Yu, X., Zhang, Z., Huang, X., Qin, W., Chen, G., Yu, F., Tang, K., et al. (2020) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2020/1517596 · Cited by 14 · see citing works
Self-citationChermside‐Scabbo, C. J., Shuster, J. T., Erdmann-Gilmore, P., Tycksen, E., Zhang, Q., Townsend, R. R., & Silva, M. J. (2024) · Aging · doi:10.18632/aging.206131 · Cited by 10 · see citing works
Vascular Pericyte-Derived Exosomes Inhibit Bone Resorption via Traf3
Cai, M., Peng, H., Liu, M., Huang, M., Zheng, W. T., Zhang, G., Lai, W., Liao, C., Cai, L., Zhang, D., et al. (2023) · International Journal of Nanomedicine · doi:10.2147/ijn.s438229 · Cited by 11 · see citing works
Wang, Y., Yang, C., Hou, Y., Wang, J., Zhang, K., Wang, L., Sun, D., Li, X., Wei, R., & Nian, H. (2024) · The FASEB Journal · doi:10.1096/fj.202302293rr · Cited by 10 · see citing works
miR-346-3p promotes osteoclastogenesis via inhibiting TRAF3 gene
Mao, Y., Chen, Y., Fu, Y., Guan, J., Liang, M., Zhu, Y., Yang, F., Li, F., Zhang, Z., Wan, C., et al. (2020) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-020-00479-w · Cited by 10 · see citing works
Che, K., Liu, X., Chi, J., Li, P., Gao, J., Fu, Z., Yan, S., Xing, X., & Hu, J. (2020) · PubMed Central · Cited by 9 · see citing works
Ling, X., Wang, X., Jing-hu, L., Zhang, T., Zhou, X., Zhou, Y., & Kang, J. (2021) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2021/7795527 · Cited by 8 · see citing works
Qi, G., Jiang, Z., Lü, W., Li, D., Chen, W., Yang, X., Ding, L., & Yuan, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1032866 · Cited by 8 · see citing works
Roles of TRAFs in Ischemia-Reperfusion Injury
Zhou, W., Lin, D., Zhong, Z., & Ye, Q. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.586487 · Cited by 7 · see citing works
TRAF3: A novel regulator of mitochondrial physiology and metabolic pathways in B lymphocytes
Jung, J., Gokhale, S., & Xie, P. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1081253 · Cited by 7 · see citing works
Liu, J., Lin, X., McDavid, A., Yang, Y., Zhang, H., Boyce, B. F., & Xing, L. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1090049 · Cited by 7 · see citing works
Self-citationNetwork Pharmacology Study to Reveal the Mechanism of Zuogui Pill for Treating Osteoporosis
Wang, G., Li, H.-L., Zhao, H., Liu, D., Chu, S., Lee, M., & Fang, Z.-B. (2023) · Current Computer - Aided Drug Design · doi:10.2174/1573409919666230302111951 · Cited by 6 · see citing works
Epigenetic Mechanisms in Osteoporosis: Exploring the Power of m6A RNA Modification
Tian, S., Song, Y., Guo, L., Hui, Z., Bai, M., & Miao, M. (2025) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.70344 · Cited by 5 · see citing works
Zhong, Y., Huang, S., Luo, P., Lai, Q., Mo, F., Yang, X., Yang, X., Zhang, B., Wei, Y., & Yang, X. (2025) · Materials & Design · doi:10.1016/j.matdes.2025.114149 · Cited by 4 · see citing works
Yang, C., Jeyaprakash, N., & Tseng, Y.-J. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c00126 · Cited by 4 · see citing works
Zhang, J., Yang, K., Chen, W., Sun, D.-L., Hu, H.-Y., Li, Q., Yan, Y., Li, Y., Yin, C., & Guo, Q. (2025) · Communications Biology · doi:10.1038/s42003-025-08175-9 · Cited by 3 · see citing works
Li, J., Fan, J., Yao, Z., Jiao, H., Duan, R., Sanders, J. O., Mesfin, A., Xing, L., & Boyce, B. F. (2026) · Bone Research · doi:10.1038/s41413-026-00525-5 · Cited by 3 · see citing works
Self-citationYang, X., Zhao, L., & Pang, Y. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1527814 · Cited by 3 · see citing works
Sun, H., Miao, Q., Wan, B., Liao, J., Tian, N., Chang, Z., Yin, J., & Zhang, X. (2025) · Journal of Nutrition · doi:10.1016/j.tjnut.2025.07.018 · Cited by 3 · see citing works
Cai, P., Yan, S., Lu, Y., Zhou, X., Wang, X., Wang, M., & Yin, Z. (2022) · Molecular Medicine Reports · doi:10.3892/mmr.2022.12741 · Cited by 3 · see citing works
RetractedLu, F., Yang, Z., Hou, N., Wang, H., Bai, S., Lu, X., Wang, Y., Lin, S., Tortorella, M. D., & Li, G. (2025) · Genes & Diseases · doi:10.1016/j.gendis.2025.101754 · Cited by 2 · see citing works
Han, K. Q., Yan, S. G., Liu, F., Li, L., Zhou, D., Lin, L., Liu, N., & Dong, J. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s544316 · Cited by 2 · see citing works
Alake, S. E., Ice, J., Robinson, K., Price, P., Hatter, B., Wozniak, K. L., Lin, D., Chowanadisai, W., Smith, B. J., & Lucas, E. A. (2024) · Physiological Reports · doi:10.14814/phy2.15914 · Cited by 2 · see citing works
Li, K., Sun, S., Gao, Y., Lu, Y., Xu, X., Chen, L., Qiao, Z., & Yang, Z. (2026) · Chinese Medical Journal · doi:10.1097/cm9.0000000000004090 · Cited by 1 · see citing works
TGFβ priming promotes TNF-induced bone erosion: a promising new target in RA?
Yao, Z., & Boyce, B. F. (2022) · Nature Reviews Rheumatology · doi:10.1038/s41584-022-00843-y · Cited by 1 · see citing works
Self-citationWang, Y., Wang, C., Gong, Y., Li, Q., Liu, M., & Sun, H. (2025) · Tissue and Cell · doi:10.1016/j.tice.2025.102790 · Cited by 1 · see citing works
Filipenko, V., Bondarenko, S., Badnaoui, A. A., Mezentsev, V., & Maltseva, V. (2021) · ORTHOPAEDICS TRAUMATOLOGY and PROSTHETICS · doi:10.15674/0030-59872020487-95
Ye, J., Hua, Z., Xiao, J., Shao, Y., Li, S., Yin, H., Wu, M., Rong, Y., Hong, B., Guo, Y., et al. (2024) · Molecular Biology Reports · doi:10.1007/s11033-024-09400-0
Ferroptosis-related genes in osteoporosis: a bioinformatics analysis and in vitro study
Yushuang, X. I. A., Wang, B., Pengfei, P. A. N., Xiangshun, R. E. N., Lixi, G. A. O., XIONG, J., & Ma, Y. (2024) · Journal of Zhejiang University (Medical Sciences) · doi:10.3724/zdxbyxb-2024-0089
Otubain 2 stabilizes TNF‑receptor associated factor 3 to accelerate bone fracture healing
Zhang, L., Guo, J., Feng, S., Zheng, Y., Wang, H., Ma, H., Chen, W., Zhang, Y., & Hou, Z. (2025) · Molecular Medicine Reports · doi:10.3892/mmr.2025.13588
Wei, E., Hu, M., Wu, L., Pan, X., Zhu, Q., Liu, H., & Liu, Y. (2024) · Figshare · doi:10.6084/m9.figshare.25939972
TGF ‐β‐Dependent α11 Integrin Expression Is Reduced in Aging Gingival Wounds
Ríos, S., Wang, Y., Valeria Muñoz, L., Narea, G., Martínez, C. L., Farías, O., López, R. P., Martínez, J. E., Hernández, P., Tobar, N., et al. (2026) · Wound Repair and Regeneration · doi:10.1111/wrr.70122
Ke, L., Yang, Y., Meng, X., Zhu, G., Yang, J., Wang, Y., Wang, X., Zhang, P., Gong, X., & Cheng, W. (2026) · Guidelines and Standards of Chinese Medicine · doi:10.1097/gscm.0000000000000086
Dong, Y., Sun, H., Zhou, J., Li, F., Yang, W., Xie, Y., Li, X., & Wang, B. (2026) · Genes & Diseases · doi:10.1016/j.gendis.2026.102109
Zhu, Z., Yang, Y., Liu, Y., & Liao, L. (2026) · Molecular Genetics and Genomics · doi:10.1007/s00438-026-02396-1
Boyce, B. F., Zuscik, M. J., & Xing, L. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-13683-2.00003-7
Self-citation
- Authors
- Li, J., Ayoub, A., Xiu, Y., Yin, X., Sanders, J. O., Mesfin, A., Xing, L., Yao, Z., & Boyce, B. F.
- Affiliations
- University of Rochester Medicine (US)
- University of Iowa (US)
- Henan University (CN)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Yao, Zhenqiang
- Boyce, Brendan F.
- ORCID
- Venue
- Nature Communications
- Published
- 2019-06-26
- Volume
- 10
- Issue
- 1
- Pages
- 2795-2795
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6595054
- OpenAlex
- W2953401387
- Cited by
- 86
- References
- 70
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 17 · 2023: 8 · 2022: 11 · 2021: 13 · 2020: 18 · 2019: 1
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (AR069655)
- National Institute on Aging (R01AG049994)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR069655, R01 AR43510, AR063650, R01AR063650, R01AR043510, P30AR069655)
- National Center for Research Resources (S10RR027340)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- TRAF3, TGF-β1, senile osteoporosis, mesenchymal progenitor cells, β-catenin degradation, GSK3β, osteogenic differentiation, NF-κB signaling, RANKL, osteoclastogenesis, bone destruction, bone formation, inflammaging
- MeSH terms
- Aging, Animals, Cell Differentiation, Female, Male, Mice, Inbred C57BL, Osteoblasts, Osteoporosis, Transforming Growth Factor beta, Mice, Knockout, TNF Receptor-Associated Factor 3, Mice, Mesenchymal Stem Cells
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