SOXC are critical regulators of adult bone mass.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 Apr 2024
05 Apr 2024
Historique:
received:
08
09
2023
accepted:
28
03
2024
medline:
6
4
2024
pubmed:
6
4
2024
entrez:
5
4
2024
Statut:
epublish
Résumé
Pivotal in many ways for human health, the control of adult bone mass is governed by complex, incompletely understood crosstalk namely between mesenchymal stem cells, osteoblasts and osteoclasts. The SOX4, SOX11 and SOX12 (SOXC) transcription factors were previously shown to control many developmental processes, including skeletogenesis, and SOX4 was linked to osteoporosis, but how SOXC control adult bone mass remains unknown. Using SOXC loss- and gain-of-function mouse models, we show here that SOXC redundantly promote prepubertal cortical bone mass strengthening whereas only SOX4 mitigates adult trabecular bone mass accrual in early adulthood and subsequent maintenance. SOX4 favors bone resorption over formation by lowering osteoblastogenesis and increasing osteoclastogenesis. Single-cell transcriptomics reveals its prevalent expression in Lepr
Identifiants
pubmed: 38580651
doi: 10.1038/s41467-024-47413-2
pii: 10.1038/s41467-024-47413-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2956Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ID : AR068308
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ID : AR072649
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ID : AR080062
Informations de copyright
© 2024. The Author(s).
Références
Liu, J., Curtis, E. M., Cooper, C. & Harvey, N. C. State of the art in osteoporosis risk assessment and treatment. J. Endocrinol. Invest. 42, 1149–1164 (2019).
pubmed: 30980341
pmcid: 6751157
doi: 10.1007/s40618-019-01041-6
Alswat, K. A. Gender disparities in osteoporosis. J. Clin. Med. Res. 9, 382–387 (2017).
pubmed: 28392857
pmcid: 5380170
doi: 10.14740/jocmr2970w
Rozenberg, S. et al. How to manage osteoporosis before the age of 50. Maturitas 138, 14–25 (2020).
pubmed: 32631584
doi: 10.1016/j.maturitas.2020.05.004
Penna, S., Capo, V., Palagano, E., Sobacchi, C. & Villa, A. One disease, many genes: implications for the treatment of osteopetroses. Front. Endocrinol. 10, 85 (2019).
doi: 10.3389/fendo.2019.00085
Bolamperti, S., Villa, I. & Rubinacci, A. Bone remodeling: an operational process ensuring survival and bone mechanical competence. Bone Res. 10, 48 (2022).
pubmed: 35851054
pmcid: 9293977
doi: 10.1038/s41413-022-00219-8
Xu, H. et al. Targeting strategies for bone diseases: signaling pathways and clinical studies. Signal. Transduct. Target. Ther. 8, 202 (2023).
pubmed: 37198232
pmcid: 10192458
doi: 10.1038/s41392-023-01467-8
Chan, W. C. W., Tan, Z., To, M. K. T. & Chan, D. Regulation and role of transcription factors in osteogenesis. Int. J. Mol. Sci. 22, 5445 (2021).
pubmed: 34064134
pmcid: 8196788
doi: 10.3390/ijms22115445
Kurotaki, D., Yoshida, H. & Tamura, T. Epigenetic and transcriptional regulation of osteoclast differentiation. Bone 138, 115471 (2020).
pubmed: 32526404
doi: 10.1016/j.bone.2020.115471
Almeida, M. et al. Estrogens and androgens in skeletal physiology and pathophysiology. Physiol. Rev. 97, 135–187 (2017).
pubmed: 27807202
doi: 10.1152/physrev.00033.2015
Wein, M. N. & Kronenberg, H. M. Regulation of bone remodeling by parathyroid hormone. Cold Spring Harb. Perspect. Med. 8, a031237 (2018).
pubmed: 29358318
pmcid: 6071549
doi: 10.1101/cshperspect.a031237
Karsenty, G. & Khosla, S. The crosstalk between bone remodeling and energy metabolism: a translational perspective. Cell Metab. 34, 805–817 (2022).
pubmed: 35545088
pmcid: 9535690
doi: 10.1016/j.cmet.2022.04.010
Tomlinson, R. E., Christiansen, B. A., Giannone, A. A. & Genetos, D. C. The role of nerves in skeletal development, adaptation, and aging. Front. Endocrinol. 11, 646 (2020).
doi: 10.3389/fendo.2020.00646
Tuckermann, J. & Adams, R. H. The endothelium-bone axis in development, homeostasis and bone and joint disease. Nat. Rev. Rheumatol. 17, 608–620 (2021).
pubmed: 34480164
pmcid: 7612477
doi: 10.1038/s41584-021-00682-3
Burkhardt, L. M. et al. The benefits of adipocyte metabolism in bone health and regeneration. Front. Cell Dev. Biol. 11, 1104709 (2023).
pubmed: 36895792
pmcid: 9988968
doi: 10.3389/fcell.2023.1104709
Shen, F., Huang, X., He, G. & Shi, Y. The emerging studies on mesenchymal progenitors in the long bone. Cell Biosci. 13, 105 (2023).
pubmed: 37301964
pmcid: 10257854
doi: 10.1186/s13578-023-01039-x
Guder, C., Gravius, S., Burger, C., Wirtz, D. C. & Schildberg, F. A. Osteoimmunology: a current update of the interplay between bone and the immune system. Front. Immunol. 11, 58 (2020).
pubmed: 32082321
pmcid: 7004969
doi: 10.3389/fimmu.2020.00058
Angelozzi, M. & Lefebvre, V. SOXopathies: growing family of developmental disorders due to SOX mutations. Trends Genet. 35, 658–671 (2019).
pubmed: 31288943
pmcid: 6956857
doi: 10.1016/j.tig.2019.06.003
Bhattaram, P. et al. Organogenesis relies on SoxC transcription factors for the survival of neural and mesenchymal progenitors. Nat. Commun. 1, 9 (2010).
pubmed: 20596238
doi: 10.1038/ncomms1008
Schilham, M. W. et al. Defects in cardiac outflow tract formation and pro-B-lymphocyte expansion in mice lacking Sox-4. Nature 380, 711–714 (1996).
pubmed: 8614465
doi: 10.1038/380711a0
Sock, E. et al. Gene targeting reveals a widespread role for the high-mobility-group transcription factor Sox11 in tissue remodeling. Mol. Cell. Biol. 24, 6635–6644 (2004).
pubmed: 15254231
pmcid: 444853
doi: 10.1128/MCB.24.15.6635-6644.2004
Bhattaram, P. et al. SOXC proteins amplify canonical WNT signaling to secure nonchondrocytic fates in skeletogenesis. J. Cell Biol. 207, 657–671 (2014).
pubmed: 25452386
pmcid: 4259807
doi: 10.1083/jcb.201405098
Kato, K., Bhattaram, P., Penzo-Mendez, A., Gadi, A. & Lefebvre, V. SOXC transcription factors induce cartilage growth plate formation in mouse embryos by promoting noncanonical WNT signaling. J. Bone Miner. Res. 30, 1560–1571 (2015).
pubmed: 25761772
doi: 10.1002/jbmr.2504
Angelozzi, M., Pellegrino da Silva, R., Gonzalez, M. V. & Lefebvre, V. Single-cell atlas of craniogenesis uncovers SOXC-dependent, highly proliferative, and myofibroblast-like osteodermal progenitors. Cell Rep. 40, 111045 (2022).
pubmed: 35830813
pmcid: 9595211
doi: 10.1016/j.celrep.2022.111045
Zawerton, A. et al. De novo SOX4 variants cause a neurodevelopmental disease associated with mild dysmorphism. Am. J. Hum. Genet. 104, 777 (2019).
pubmed: 30951678
pmcid: 6451692
doi: 10.1016/j.ajhg.2019.01.014
Angelozzi, M. et al. Consolidation of the clinical and genetic definition of a SOX4-related neurodevelopmental syndrome. J. Med. Genet. 59, 1058–1068 (2022).
pubmed: 35232796
doi: 10.1136/jmedgenet-2021-108375
Tsurusaki, Y. et al. De novo SOX11 mutations cause Coffin-Siris syndrome. Nat. Commun. 5, 4011 (2014).
pubmed: 24886874
doi: 10.1038/ncomms5011
Duncan, E. L. et al. Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk. PLoS Genet. 7, e1001372 (2011).
pubmed: 21533022
pmcid: 3080863
doi: 10.1371/journal.pgen.1001372
Li, G., Gu, Z., He, Y., Wang, C. & Duan, J. The effect of SOX4 gene 3’UTR polymorphisms on osteoporosis. J. Orthop. Surg. Res. 16, 321 (2021).
pubmed: 34006298
pmcid: 8130251
doi: 10.1186/s13018-021-02454-x
Jemtland, R. et al. Molecular disease map of bone characterizing the postmenopausal osteoporosis phenotype. J. Bone Miner. Res. 26, 1793–1801 (2011).
pubmed: 21452281
doi: 10.1002/jbmr.396
Nissen-Meyer, L. S. et al. Osteopenia, decreased bone formation and impaired osteoblast development in Sox4 heterozygous mice. J. Cell Sci. 120, 2785–2795 (2007).
pubmed: 17652162
doi: 10.1242/jcs.003855
Gadi, J. et al. The transcription factor protein Sox11 enhances early osteoblast differentiation by facilitating proliferation and the survival of mesenchymal and osteoblast progenitors. J. Biol. Chem. 288, 25400–25413 (2013).
pubmed: 23888050
pmcid: 3757203
doi: 10.1074/jbc.M112.413377
Davey, R. A. et al. Decreased body weight in young Osterix-Cre transgenic mice results in delayed cortical bone expansion and accrual. Transgenic Res. 21, 885–893 (2012).
pubmed: 22160436
doi: 10.1007/s11248-011-9581-z
Seeman, E. Age- and menopause-related bone loss compromise cortical and trabecular microstructure. J. Gerontol. A Biol. Sci. Med. Sci. 68, 1218–1225 (2013).
pubmed: 23833200
doi: 10.1093/gerona/glt071
Tower, R. J., Campbell, G. M., Muller, M., Gluer, C. C. & Tiwari, S. Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate site-specific changes in bone metabolism in vivo. Bone 74, 171–181 (2015).
pubmed: 25613175
doi: 10.1016/j.bone.2015.01.009
Zhong, L. et al. Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment. Elife 9, e54695 (2020).
pubmed: 32286228
pmcid: 7220380
doi: 10.7554/eLife.54695
Baccin, C. et al. Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization. Nat. Cell Biol. 22, 38–48 (2020).
pubmed: 31871321
doi: 10.1038/s41556-019-0439-6
Zhang, H. et al. Sox4 is a key oncogenic target in C/EBPalpha mutant acute myeloid leukemia. Cancer Cell 24, 575–588 (2013).
pubmed: 24183681
pmcid: 4038627
doi: 10.1016/j.ccr.2013.09.018
Sun, B. et al. Sox4 is required for the survival of pro-B cells. J. Immunol. 190, 2080–2089 (2013).
pubmed: 23345330
doi: 10.4049/jimmunol.1202736
Tsang, K. Y. & Cheah, K. S. The extended chondrocyte lineage: implications for skeletal homeostasis and disorders. Curr. Opin. Cell Biol. 61, 132–140 (2019).
pubmed: 31541943
doi: 10.1016/j.ceb.2019.07.011
Long, J. T. et al. Hypertrophic chondrocytes serve as a reservoir for marrow-associated skeletal stem and progenitor cells, osteoblasts, and adipocytes during skeletal development. Elife 11, e76932 (2022).
pubmed: 35179487
pmcid: 8893718
doi: 10.7554/eLife.76932
Chen, J. et al. Osx-Cre targets multiple cell types besides osteoblast lineage in postnatal mice. PLoS ONE 9, e85161 (2014).
pubmed: 24454809
pmcid: 3893188
doi: 10.1371/journal.pone.0085161
Morikawa, S. et al. Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J. Exp. Med. 206, 2483–2496 (2009).
pubmed: 19841085
pmcid: 2768869
doi: 10.1084/jem.20091046
Mo, C. et al. Single-cell transcriptomics of LepR-positive skeletal cells reveals heterogeneous stress-dependent stem and progenitor pools. EMBO J. 41, e108415 (2022).
pubmed: 34957577
doi: 10.15252/embj.2021108415
Aibar, S. et al. SCENIC: single-cell regulatory network inference and clustering. Nat. Methods 14, 1083–1086 (2017).
pubmed: 28991892
pmcid: 5937676
doi: 10.1038/nmeth.4463
Neunaber, C. et al. Increased trabecular bone formation in mice lacking the growth factor midkine. J. Bone Miner. Res. 25, 1724–1735 (2010).
pubmed: 20200993
doi: 10.1002/jbmr.75
Jin, Q. Y. et al. Follistatin-like 1 suppresses osteoblast differentiation of bone marrow mesenchymal cells during inflammation. Arch. Oral Biol. 135, 105345 (2022).
pubmed: 35026647
doi: 10.1016/j.archoralbio.2022.105345
Bodine, P. V. et al. The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice. Mol. Endocrinol. 18, 1222–1237 (2004).
pubmed: 14976225
doi: 10.1210/me.2003-0498
Kim, H. et al. Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism. Proc. Natl Acad. Sci. USA 115, E11128–E11137 (2018).
pubmed: 30385632
pmcid: 6255152
doi: 10.1073/pnas.1814044115
Zhang, Z., Jiang, W., Hu, M., Gao, R. & Zhou, X. MiR-486-3p promotes osteogenic differentiation of BMSC by targeting CTNNBIP1 and activating the Wnt/beta-catenin pathway. Biochem. Biophys. Res. Commun. 566, 59–66 (2021).
pubmed: 34118593
doi: 10.1016/j.bbrc.2021.05.098
Palmer, G. D. et al. F-spondin deficient mice have a high bone mass phenotype. PLoS ONE 9, e98388 (2014).
pubmed: 24875054
pmcid: 4038615
doi: 10.1371/journal.pone.0098388
Zou, W. et al. Ablation of fat cells in adult mice induces massive bone gain. Cell Metab. 32, 801–813.e806 (2020).
pubmed: 33027637
pmcid: 7642038
doi: 10.1016/j.cmet.2020.09.011
Lee, E. J. et al. PTX3 stimulates osteoclastogenesis by increasing osteoblast RANKL production. J .Cell Physiol. 229, 1744–1752 (2014).
pubmed: 24664887
doi: 10.1002/jcp.24626
Yang, Y. Q. et al. The role of vascular endothelial growth factor in ossification. Int. J. Oral Sci. 4, 64–68 (2012).
pubmed: 22722639
pmcid: 3412670
doi: 10.1038/ijos.2012.33
Danjo, A. et al. Cystatin C stimulates the differentiation of mouse osteoblastic cells and bone formation. Biochem. Biophys. Res. Commun. 360, 199–204 (2007).
pubmed: 17592728
doi: 10.1016/j.bbrc.2007.06.028
Lerner, U. H. et al. Cystatin C, and inhibitor of bone resorption produced by osteoblasts. Acta Physiol. Scand. 161, 81–92 (1997).
pubmed: 9381954
doi: 10.1046/j.1365-201X.1997.d01-1933.x
Yu, B. et al. Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-kappaB. Nat. Med 20, 1009–1017 (2014).
pubmed: 25108526
pmcid: 4159424
doi: 10.1038/nm.3586
Simic, P. et al. Systemically administered bone morphogenetic protein-6 restores bone in aged ovariectomized rats by increasing bone formation and suppressing bone resorption. J. Biol. Chem. 281, 25509–25521 (2006).
pubmed: 16798745
doi: 10.1074/jbc.M513276200
Behonick, D. J. et al. Role of matrix metalloproteinase 13 in both endochondral and intramembranous ossification during skeletal regeneration. PLoS ONE 2, e1150 (2007).
pubmed: 17987127
pmcid: 2063465
doi: 10.1371/journal.pone.0001150
Berezovska, O. et al. Osteocalcin affects bone mineral and mechanical properties in female mice. Bone 128, 115031 (2019).
pubmed: 31401301
pmcid: 8243730
doi: 10.1016/j.bone.2019.08.004
Si, J., Wang, C., Zhang, D., Wang, B. & Zhou, Y. Osteopontin in Bone Metabolism and Bone Diseases. Med. Sci. Monit. 26, e919159 (2020).
pubmed: 31996665
pmcid: 7003659
doi: 10.12659/MSM.919159
Zhang, J. et al. Matrix Gla Protein Promotes the Bone Formation by Up-Regulating Wnt/beta-Catenin Signaling Pathway. Front. Endocrinol. 10, 891 (2019).
doi: 10.3389/fendo.2019.00891
Chen, P. C., Cheng, H. C., Yang, S. F., Lin, C. W. & Tang, C. H. The CCN family proteins: modulators of bone development and novel targets in bone-associated tumors. Biomed. Res. Int. 2014, 437096 (2014).
pubmed: 24551846
pmcid: 3914550
Yanaka, N. et al. Novel membrane protein containing glycerophosphodiester phosphodiesterase motif is transiently expressed during osteoblast differentiation. J. Biol. Chem. 278, 43595–43602 (2003).
pubmed: 12933806
doi: 10.1074/jbc.M302867200
Roberts, F., Zhu, D., Farquharson, C. & Macrae, V. E. ENPP1 in the regulation of mineralization and beyond. Trends Biochem. Sci. 44, 616–628 (2019).
pubmed: 30799235
doi: 10.1016/j.tibs.2019.01.010
Yuan, B. et al. Aberrant Phex function in osteoblasts and osteocytes alone underlies murine X-linked hypophosphatemia. J. Clin. Invest. 118, 722–734 (2008).
pubmed: 18172553
pmcid: 2157563
Platanias, L. C. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat. Rev. Immunol. 5, 375–386 (2005).
pubmed: 15864272
doi: 10.1038/nri1604
Brylka, L. J. & Schinke, T. Chemokines in physiological and pathological bone remodeling. Front. Immunol. 10, 2182 (2019).
pubmed: 31572390
pmcid: 6753917
doi: 10.3389/fimmu.2019.02182
Pinney, D. F. & Emerson, C. P. Jr. 10T1/2 cells: an in vitro model for molecular genetic analysis of mesodermal determination and differentiation. Environ. Health Perspect. 80, 221–227 (1989).
pubmed: 2466641
pmcid: 1567628
doi: 10.1289/ehp.8980221
Janky, R. et al. iRegulon: from a gene list to a gene regulatory network using large motif and track collections. PLoS Comput. Biol. 10, e1003731 (2014).
pubmed: 25058159
pmcid: 4109854
doi: 10.1371/journal.pcbi.1003731
Osterhoff, G. et al. Bone mechanical properties and changes with osteoporosis. Injury 47, S11–S20 (2016).
pubmed: 27338221
pmcid: 4955555
doi: 10.1016/S0020-1383(16)47003-8
Baryawno, N. et al. A cellular taxonomy of the bone marrow stroma in homeostasis and leukemia. Cell 177, 1915–1932.e1916 (2019).
pubmed: 31130381
pmcid: 6570562
doi: 10.1016/j.cell.2019.04.040
Tikhonova, A. N. et al. The bone marrow microenvironment at single-cell resolution. Nature 569, 222–228 (2019).
pubmed: 30971824
pmcid: 6607432
doi: 10.1038/s41586-019-1104-8
Yu, W. et al. Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss. J. Clin. Invest. 131, e140214 (2021).
pubmed: 33206630
pmcid: 7810488
doi: 10.1172/JCI140214
Zhong, L. et al. Csf1 from marrow adipogenic precursors is required for osteoclast formation and hematopoiesis in bone. Elife 12, e82112 (2023).
pubmed: 36779854
pmcid: 10005765
doi: 10.7554/eLife.82112
Zhou, B. O., Yue, R., Murphy, M. M., Peyer, J. G. & Morrison, S. J. Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell 15, 154–168 (2014).
pubmed: 24953181
pmcid: 4127103
doi: 10.1016/j.stem.2014.06.008
Shu, H. S. et al. Tracing the skeletal progenitor transition during postnatal bone formation. Cell Stem Cell 28, 2122–2136.e2123 (2021).
pubmed: 34499868
doi: 10.1016/j.stem.2021.08.010
Maruyama, K., Muramatsu, H., Ishiguro, N. & Muramatsu, T. Midkine, a heparin-binding growth factor, is fundamentally involved in the pathogenesis of rheumatoid arthritis. Arthritis Rheumatol. 50, 1420–1429 (2004).
doi: 10.1002/art.20175
Rittling, S. R. et al. Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro. J. Bone Miner. Res. 13, 1101–1111 (1998).
pubmed: 9661074
doi: 10.1359/jbmr.1998.13.7.1101
Chang, J. et al. Noncanonical Wnt-4 signaling enhances bone regeneration of mesenchymal stem cells in craniofacial defects through activation of p38 MAPK. J. Biol. Chem. 282, 30938–30948 (2007).
pubmed: 17720811
doi: 10.1074/jbc.M702391200
Tang, M., Tian, L., Luo, G. & Yu, X. Interferon-gamma-mediated osteoimmunology. Front. Immunol. 9, 1508 (2018).
pubmed: 30008722
pmcid: 6033972
doi: 10.3389/fimmu.2018.01508
Kim, S. et al. Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation. Genes Dev. 17, 1979–1991 (2003).
pubmed: 12923053
pmcid: 196253
doi: 10.1101/gad.1119303
Hopwood, B., Tsykin, A., Findlay, D. M. & Fazzalari, N. L. Gene expression profile of the bone microenvironment in human fragility fracture bone. Bone 44, 87–101 (2009).
pubmed: 18840552
doi: 10.1016/j.bone.2008.08.120
Sul, O. J. et al. Absence of MCP-1 leads to elevated bone mass via impaired actin ring formation. J. Cell Physiol. 227, 1619–1627 (2012).
pubmed: 21678414
doi: 10.1002/jcp.22879
Binder, N. B. et al. Estrogen-dependent and C-C chemokine receptor-2-dependent pathways determine osteoclast behavior in osteoporosis. Nat. Med. 15, 417–424 (2009).
pubmed: 19330010
doi: 10.1038/nm.1945
Phan, Q. T. et al. Cxcl9l and Cxcr3.2 regulate recruitment of osteoclast progenitors to bone matrix in a medaka osteoporosis model. Proc. Natl Acad. Sci. USA 117, 19276–19286 (2020).
pubmed: 32719141
pmcid: 7431079
doi: 10.1073/pnas.2006093117
Liu, Z. et al. Increased osteoblastic Cxcl9 contributes to the uncoupled bone formation and resorption in postmenopausal osteoporosis. Clin. Interv. Aging 15, 1201–1212 (2020).
pubmed: 32764906
pmcid: 7381095
doi: 10.2147/CIA.S254885
Liu, P. et al. Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis. Cell Death Differ. 24, 672–682 (2017).
pubmed: 28106886
pmcid: 5384024
doi: 10.1038/cdd.2016.165
Gao, Y. et al. IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation. J. Clin. Invest. 117, 122–132 (2007).
pubmed: 17173138
doi: 10.1172/JCI30074
Franceschi, C. et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci. 908, 244–254 (2000).
pubmed: 10911963
doi: 10.1111/j.1749-6632.2000.tb06651.x
Moreno, C. S. SOX4: the unappreciated oncogene. Semin. Cancer Biol. 67, 57–64 (2020).
pubmed: 31445218
doi: 10.1016/j.semcancer.2019.08.027
Zhang, L. et al. Suppression of Sox4 protects against myocardial ischemic injury by reduction of cardiac apoptosis in mice. J. Cell Physiol. 236, 1094–1104 (2021).
pubmed: 32657438
doi: 10.1002/jcp.29918
Collins, S. C. et al. Increased expression of the diabetes gene SOX4 reduces insulin secretion by impaired fusion pore expansion. Diabetes 65, 1952–1961 (2016).
pubmed: 26993066
doi: 10.2337/db15-1489
Bhattaram, P., Muschler, G., Wixler, V. & Lefebvre, V. Inflammatory cytokines stabilize SOXC transcription factors to mediate the transformation of fibroblast-like synoviocytes in arthritic disease. Arthritis Rheumatol. 70, 371–382 (2018).
pubmed: 29193895
pmcid: 5826855
doi: 10.1002/art.40386
Takahata, Y. et al. Sox4 is involved in osteoarthritic cartilage deterioration through induction of ADAMTS4 and ADAMTS5. FASEB J. 33, 619–630 (2019).
pubmed: 30016600
doi: 10.1096/fj.201800259R
Gupta, S. et al. Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism. Proc. Natl Acad. Sci. USA 117, 16481–16491 (2020).
pubmed: 32601182
pmcid: 7368314
doi: 10.1073/pnas.2003603117
Pujantell, M. & Altfeld, M. Consequences of sex differences in Type I IFN responses for the regulation of antiviral immunity. Front. Immunol. 13, 986840 (2022).
pubmed: 36189206
pmcid: 9522975
doi: 10.3389/fimmu.2022.986840
Webb, K. et al. Sex and pubertal differences in the type 1 interferon pathway associate with both x chromosome number and serum sex hormone concentration. Front. Immunol. 9, 3167 (2018).
pubmed: 30705679
doi: 10.3389/fimmu.2018.03167
Yuan, S. G. et al. Bindarit reduces bone loss in ovariectomized mice by inhibiting CCL2 and CCL7 expression via the NF-kappaB signaling pathway. Orthop. Surg. 14, 1203–1216 (2022).
pubmed: 35470579
pmcid: 9163972
doi: 10.1111/os.13252
Yang, X. W. et al. Elevated CCL2/MCP-1 levels are related to disease severity in postmenopausal osteoporotic patients. Clin. Lab. 62, 2173–2181 (2016).
pubmed: 28164676
doi: 10.7754/Clin.Lab.2016.160408
Shigehara, K., Izumi, K., Kadono, Y. & Mizokami, A. Testosterone and bone health in men: a narrative review. J. Clin. Med. 10, 530 (2021).
pubmed: 33540526
pmcid: 7867125
doi: 10.3390/jcm10030530
Noh, T. et al. Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner. PLoS ONE 4, e5438 (2009).
pubmed: 19412553
pmcid: 2673053
doi: 10.1371/journal.pone.0005438
Albiol, L. et al. Effects of long-term sclerostin deficiency on trabecular bone mass and adaption to limb loading differ in male and female mice. Calcif. Tissue Int. 106, 415–430 (2020).
pubmed: 31873756
doi: 10.1007/s00223-019-00648-4
Choi, R. B. & Robling, A. G. The Wnt pathway: an important control mechanism in bone’s response to mechanical loading. Bone 153, 116087 (2021).
pubmed: 34271473
pmcid: 8478810
doi: 10.1016/j.bone.2021.116087
Liu, X. H., Kirschenbaum, A., Yao, S. & Levine, A. C. Androgens promote preosteoblast differentiation via activation of the canonical Wnt signaling pathway. Ann. N. Y. Acad. Sci. 1116, 423–431 (2007).
pubmed: 17646262
doi: 10.1196/annals.1402.017
Penzo-Mendez, A., Dy, P., Pallavi, B. & Lefebvre, V. Generation of mice harboring a Sox4 conditional null allele. Genesis 45, 776–780 (2007).
pubmed: 18064674
doi: 10.1002/dvg.20358
Logan, M. et al. Expression of Cre Recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis 33, 77–80 (2002).
pubmed: 12112875
doi: 10.1002/gene.10092
Rodda, S. J. & McMahon, A. P. Distinct roles for hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 133, 3231–3244 (2006).
pubmed: 16854976
doi: 10.1242/dev.02480
Gebhard, S. et al. Specific expression of Cre recombinase in hypertrophic cartilage under the control of a BAC-Col10a1 promoter. Matrix Biol. 27, 693–699 (2008).
pubmed: 18692570
pmcid: 4013020
doi: 10.1016/j.matbio.2008.07.001
Henry, S. P. et al. Generation of aggrecan-CreERT2 knockin mice for inducible Cre activity in adult cartilage. Genesis 47, 805–814 (2009).
pubmed: 19830818
pmcid: 3951921
doi: 10.1002/dvg.20564
Sophocleous, A. & Idris, A. I. Ovariectomy/orchiectomy in rodents. Methods Mol. Biol. 1914, 261–267 (2019).
pubmed: 30729469
doi: 10.1007/978-1-4939-8997-3_13
Zambrowicz, B. P. et al. Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. Proc. Natl Acad. Sci. USA 94, 3789–3794 (1997).
pubmed: 9108056
pmcid: 20519
doi: 10.1073/pnas.94.8.3789
Chu, V. T. et al. Efficient generation of Rosa26 knock-in mice using CRISPR/Cas9 in C57BL/6 zygotes. BMC Biotechnol. 16, 4 (2016).
pubmed: 26772810
pmcid: 4715285
doi: 10.1186/s12896-016-0234-4
Srinivas, S. et al. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev. Biol. 1, 4 (2001).
pubmed: 11299042
pmcid: 31338
doi: 10.1186/1471-213X-1-4
Niwa, H., Yamamura, K. & Miyazaki, J. Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108, 193–199 (1991).
pubmed: 1660837
doi: 10.1016/0378-1119(91)90434-D
Wheeler, R. L., Hampton, A. D. & Langley, N. R. The effects of body mass index and age on cross-sectional properties of the femoral neck. Clin. Anat. 28, 1048–1057 (2015).
pubmed: 26385008
doi: 10.1002/ca.22632
Masson, P. Some histological methods. Trichrome stainings and their preliminary technique. J. Tech. Meth. 12, 75–90 (1929).
Cole, A. A. & Walters, L. M. Tartrate-resistant acid phosphatase in bone and cartilage following decalcification and cold-embedding in plastic. J. Histochem. Cytochem. 35, 203–206 (1987).
pubmed: 3540104
doi: 10.1177/35.2.3540104
de Charleroy, C., Haseeb, A. & Lefebvre, V. Preparation of adult mouse skeletal tissue sections for RNA in situ hybridization. Methods Mol. Biol. 2245, 85–92 (2021).
pubmed: 33315196
pmcid: 9063681
doi: 10.1007/978-1-0716-1119-7_6
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587.e3529 (2021).
pubmed: 34062119
pmcid: 8238499
doi: 10.1016/j.cell.2021.04.048
McGinnis, C. S., Murrow, L. M. & Gartner, Z. J. DoubletFinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors. Cell Syst. 8, 329–337.e324 (2019).
pubmed: 30954475
pmcid: 6853612
doi: 10.1016/j.cels.2019.03.003
Wu, T. et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation 2, 100141 (2021).
pubmed: 34557778
pmcid: 8454663
Street, K. et al. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics 19, 477 (2018).
pubmed: 29914354
pmcid: 6007078
doi: 10.1186/s12864-018-4772-0
La Manno, G. et al. RNA velocity of single cells. Nature 560, 494–498 (2018).
pubmed: 30089906
pmcid: 6130801
doi: 10.1038/s41586-018-0414-6
Bergen, V., Lange, M., Peidli, S., Wolf, F. A. & Theis, F. J. Generalizing RNA velocity to transient cell states through dynamical modeling. Nat. Biotechnol. 38, 1408–1414 (2020).
pubmed: 32747759
doi: 10.1038/s41587-020-0591-3
Li, S. et al. A relay velocity model infers cell-dependent RNA velocity. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-01728-5 (2023).
doi: 10.1038/s41587-023-01728-5
pubmed: 38082081
pmcid: 10791576