Guinea Pig

Mechanisms of bone development and repair

1.Ambrosi, T. H., Longaker, M. T. & Chan, C. K. F. A revised perspective of skeletal stem cell biology. Front. Cell Dev. Biol. 7, 189 (2019).PubMed 
PubMed Central 

Google Scholar 
2.Murphy, M. P. et al. The role of skeletal stem cells in the reconstruction of bone defects. J. Craniofac. Surg. 28, 1136–1141 (2017).PubMed 
PubMed Central 

Google Scholar 
3.Long, F. Building strong bones: molecular regulation of the osteoblast lineage. Nat. Rev. Mol. Cell Biol. 13, 27–38 (2012).CAS 

Google Scholar 
4.Bianco, P. & Robey, P. G. Skeletal stem cells. Development 142, 1023–1027 (2015).CAS 
PubMed 
PubMed Central 

Google Scholar 
5.Garnero, P., Sornay-Rendu, E., Chapuy, M. C. & Delmas, P. D. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J. Bone Miner. Res. 11, 337–349 (2009).
Google Scholar 
6.Soltanoff, C. S., Yang, S., Chen, W. & Li, Y. P. Signaling networks that control the lineage commitment and differentiation of bone cells. Crit. Rev. Eukaryot. Gene Expr. 19, 1–46 (2009).CAS 
PubMed 
PubMed Central 

Google Scholar 
7.Compton, J. T. & Lee, F. Y. Current concepts review: a review of osteocyte function and the emerging importance of sclerostin. J. Bone Joint Surg. Am. 96, 1659–1668 (2014).PubMed 
PubMed Central 

Google Scholar 
8.Van Bezooijen, R. L. et al. Sclerostin Is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J. Exp. Med. 199, 805–814 (2004).PubMed 
PubMed Central 

Google Scholar 
9.Robling, A. G. et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J. Biol. Chem. 283, 5866–5875 (2008).CAS 
PubMed 

Google Scholar 
10.Tatsumi, S. et al. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 5, 464–475 (2007).CAS 
PubMed 

Google Scholar 
11.Jacome-Galarza, C. E., Lee, S. K., Lorenzo, J. A. & Aguila, H. L. Identification, characterization, and isolation of a common progenitor for osteoclasts, macrophages, and dendritic cells from murine bone marrow and periphery. J. Bone Miner. Res. 28, 1203–1213 (2013).CAS 
PubMed 
PubMed Central 

Google Scholar 
12.Kong, Y. Y. et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397, 315–323 (1999).CAS 
PubMed 

Google Scholar 
13.Dougall, W. C. et al. RANK is essential for osteoclast and lymph node development. Genes. Dev. 13, 2412–2424 (1999).CAS 
PubMed 
PubMed Central 

Google Scholar 
14.Xu, F. & Teitelbaum, S. L. Osteoclasts: new insights. Bone Res. 1, 11–26 (2013).CAS 
PubMed Central 

Google Scholar 
15.Meyers, C. et al. Heterotopic ossification: a comprehensive review. JBMR Plus 3, e10172 (2019).PubMed 
PubMed Central 

Google Scholar 
16.Dallas, S. L., Xie, Y., Shiflett, L. A. & Ueki, Y. Mouse Cre models for the study of bone diseases. Curr. Osteoporos. Rep. 16, 466–477 (2018).PubMed 
PubMed Central 

Google Scholar 
17.Pittenger, M. F. et al. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143–147 (1999). This work establishes the potential for MSCs to differentiate into bone, cartilage and fat.CAS 
PubMed 

Google Scholar 
18.Chen, Q. et al. Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? Cell Death Differ. 23, 1128–1139 (2016).CAS 
PubMed 
PubMed Central 

Google Scholar 
19.Friedenstein, A. J., Chailakhjan, R. K. & Lalykina, K. S. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Prolif. 3, 393–403 (1970).CAS 

Google Scholar 
20.Friedenstein, A. J., Chailakhyan, R. K. & Gerasimov, U. V. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Prolif. 20, 263–272 (1987).CAS 

Google Scholar 
21.Friedenstein, A. J. Osteogenic stem cells in the bone marrow. Bone Miner. Res. https://doi.org/10.1016/b978-0-444-81371-8.50012-1 (1990).
Google Scholar 
22.Wei, J. et al. Glucose uptake and Runx2 synergize to orchestrate osteoblast differentiation and bone formation. Cell 161, 1576–1591 (2015).CAS 
PubMed 
PubMed Central 

Google Scholar 
23.Wang, T., Zhang, X. & Bikle, D. D. Osteogenic differentiation of periosteal cells during fracture healing. J. Cell Physiol. 232, 913–921 (2017).CAS 
PubMed 

Google Scholar 
24.Ackema, K. B. & Charité, J. Mesenchymal stem cells from different organs are characterized by distinct topographic Hox codes. Stem Cell Dev. 17, 979–991 (2008).CAS 

Google Scholar 
25.Rux, D. R. et al. Regionally restricted Hox function in adult bone marrow multipotent mesenchymal stem/stromal cells. Dev. Cell 39, 653–666 (2016).CAS 
PubMed 
PubMed Central 

Google Scholar 
26.Nelson, L. T., Rakshit, S., Sun, H. & Wellik, D. M. Generation and expression of a Hoxa11eGFP targeted allele in mice. Dev. Dyn. 237, 3410–3416 (2008).CAS 
PubMed 
PubMed Central 

Google Scholar 
27.Swinehart, I. T., Schlientz, A. J., Quintanilla, C. A., Mortlock, D. P. & Wellik, D. M. Hox11 genes are required for regional patterning and integration of muscle, tendon and bone. Development 140, 4574–4582 (2013).CAS 
PubMed 
PubMed Central 

Google Scholar 
28.Pineault, K. M., Song, J. Y., Kozloff, K. M., Lucas, D. & Wellik, D. M. Hox11 expressing regional skeletal stem cells are progenitors for osteoblasts, chondrocytes and adipocytes throughout life. Nat. Commun. 10, 3168 (2019).PubMed 
PubMed Central 

Google Scholar 
29.Rux, D. R. & Wellik, D. M. Hox genes in the adult skeleton: novel functions beyond embryonic development. Dev. Dyn. 246, 310–317 (2017).CAS 
PubMed 
PubMed Central 

Google Scholar 
30.Chan, C. K. F. et al. Identification and specification of the mouse skeletal stem cell. Cell 160, 285–298 (2015). The work is the first to isolate the SSC in mice, which has the differentiation capacity to be restricted to bone, cartilage,and bone stroma.CAS 
PubMed 
PubMed Central 

Google Scholar 
31.Chan, C. K. F. et al. Identification of the human skeletal stem cell. Cell 175, 43–56 (2018).CAS 
PubMed 
PubMed Central 

Google Scholar 
32.Sacchetti, B. et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131, 324–336 (2007).CAS 
PubMed 

Google Scholar 
33.Kassem, M. & Bianco, P. Skeletal stem cells in space and time. Cell 160, 17–19 (2015).CAS 
PubMed 

Google Scholar 
34.Bianco, P. Stem cells and bone: a historical perspective. Bone 70, 2–9 (2015).PubMed 

Google Scholar 
35.Ueno, H. & Weissman, I. L. Clonal analysis of mouse development reveals a polyclonal origin for yolk sac blood islands. Dev. Cell 11, 519–533 (2006).CAS 
PubMed 

Google Scholar 
36.Worthley, D. L. et al. Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. Cell 160, 269–284 (2015).CAS 
PubMed 
PubMed Central 

Google Scholar 
37.Chan, C. K. F. et al. Clonal precursor of bone, cartilage, and hematopoietic niche stromal cells. Proc. Natl Acad. Sci. USA 110, 12643–12648 (2013).CAS 
PubMed 

Google Scholar 
38.Berendsen, A. D. & Olsen, B. R. Bone development. Bone 80, 14–18 (2015).CAS 
PubMed 
PubMed Central 

Google Scholar 
39.Marecic, O. et al. Identification and characterization of an injury-induced skeletal progenitor. Proc. Natl Acad. Sci. USA 112, 9920–9925 (2015).CAS 
PubMed 

Google Scholar 
40.Tevlin, R. et al. Pharmacological rescue of diabetic skeletal stem cell niches. Sci. Transl Med. 9, eaag2809 (2017).PubMed 
PubMed Central 

Google Scholar 
41.Ransom, R. C. et al. Mechanoresponsive stem cells acquire neural crest fate in jaw regeneration. Nature 563, 514–521 (2018).CAS 
PubMed 
PubMed Central 

Google Scholar 
42.Mizuhashi, K. et al. Resting zone of the growth plate houses a unique class of skeletal stem cells. Nature 563, 254–258 (2018).CAS 
PubMed 
PubMed Central 

Google Scholar 
43.Debnath, S. et al. Discovery of a periosteal stem cell mediating intramembranous bone formation. Nature 562, 133–139 (2018).CAS 
PubMed 
PubMed Central 

Google Scholar 
44.Jia, G. et al. Single cell RNA-seq and ATAC-seq analysis of cardiac progenitor cell transition states and lineage settlement. Nat. Commun. 9, 4877 (2018).PubMed 
PubMed Central 

Google Scholar 
45.Baker, S., Rogerson, C., Hayes, A., Sharrocks, A. & Rattray, M. Classifying cells with Scasat, a single-cell ATAC-seq analysis tool. Nucleic Acids Res. 47, e10 (2019).PubMed 

Google Scholar 
46.Le Douarin, N. M. & Smith, J. Development of the peripheral nervous system from the neural crest. Annu. Rev. Cell Biol. 4, 375–404 (1988).PubMed 

Google Scholar 
47.Long, F. & Ornitz, D. M. Development of the endochondral skeleton. Cold Spring Harb Perspect. Biol. 5, a008334 (2013).PubMed 
PubMed Central 

Google Scholar 
48.Kronenberg, H. M. Developmental regulation of the growth plate. Nature. 423, 332–336 (2003).CAS 
PubMed 

Google Scholar 
49.Maes, C. & Kronenberg, H. M. Postnatal bone growth: growth plate biology, bone formation, and remodeling. pediatric. Bone https://doi.org/10.1016/B978-0-12-382040-2.10004-8 (2012).
Google Scholar 
50.Lefebvr, E. V. & Dvir-Ginzberg, M. SOX9 and the many facets of its regulation in the chondrocyte lineage. Connect. Tissue Res. 58, 2–14 (2017).
Google Scholar 
51.Lovell-Badge, R. The early history of the Sox genes. Int. J. Biochem. Cell Biol. 42, 378–380 (2010).CAS 
PubMed 

Google Scholar 
52.Bi, W., Deng, J. M., Zhang, Z., Behringer, R. R. & De Crombrugghe, B. Sox9 is required for cartilage formation. Nat. Genet. 22, 85–89 (1999).CAS 
PubMed 

Google Scholar 
53.Akiyama, H., Chaboissier, M. C., Martin, J. F., Schedl, A. & De Crombrugghe, B. The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev. 16, 2813–2828 (2002).CAS 
PubMed 
PubMed Central 

Google Scholar 
54.Henry, S. P., Liang, S., Akdemir, K. C. & De Crombrugghe, B. The postnatal role of Sox9 in cartilage. J. Bone Miner. Res. 27, 2511–2525 (2012).CAS 
PubMed 
PubMed Central 

Google Scholar 
55.Schafer, A. J. et al. Campomelic dysplasia with XY sex reversal: diverse phenotypes resulting from mutations in a single gene. Ann. N. Y. Acad. Sci. 785, 137–149 (1996).CAS 
PubMed 

Google Scholar 
56.Gentilin, B. et al. Phenotype of five cases of prenatally diagnosed campomelic dysplasia harboring novel mutations of the SOX9 gene. Ultrasound Obstet. Gynecol. 36, 315–323 (2010).CAS 
PubMed 

Google Scholar 
57.Komori, T. Regulation of bone development and extracellular matrix protein genes by RUNX2. Cell Tissue Res. 339, 189–195 (2010).CAS 
PubMed 

Google Scholar 
58.Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L. & Karsenty, G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89, 747–754 (1997).CAS 

Google Scholar 
59.Harada, H. et al. Cbfa1 isoforms exert functional differences in osteoblast differentiation. J. Biol. Chem. 274, 6972–6978 (1999).CAS 
PubMed 

Google Scholar 
60.Komori, T. et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89, 755–764 (1997). This work establishes RUNX2 as an essential transcription factor for osteoblast differentiation.CAS 
PubMed 

Google Scholar 
61.Otto, F. et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89, 765–771 (1997).CAS 
PubMed 

Google Scholar 
62.Inada, M. et al. Maturational disturbance of chondrocytes in Cbfa1-deficient mice. Dev. Dyn. 214, 279–290 (1999).CAS 
PubMed 

Google Scholar 
63.Takarada, T. et al. An analysis of skeletal development in osteoblast-specific and chondrocyte-specific runt-related transcription factor-2 (Runx2) knockout mice. J. Bone Miner. Res. 28, 2064–2069 (2013).CAS 
PubMed 

Google Scholar 
64.Maruyama, Z. et al. Runx2 determines bone maturity and turnover rate in postnatal bone development and is involved in bone loss in estrogen deficiency. Dev. Dyn. 236, 1876–1890 (2007).CAS 
PubMed 

Google Scholar 
65.Sinha, K. M. & Zhou, X. Genetic and molecular control of osterix in skeletal formation. J. Cell Biochem. 114, 975–984 (2013).CAS 
PubMed 
PubMed Central 

Google Scholar 
66.Karsenty, G. Minireview: tranzscriptional control of osteoblast differentiation. Endocrinology 142, 2731–2733 (2001).CAS 
PubMed 

Google Scholar 
67.Nakashima, K. & De Crombrugghe, B. Transcriptional mechanisms in osteoblast differentiation and bone formation. Trends Genet. 19, 458–466 (2003).CAS 
PubMed 

Google Scholar 
68.Nakashima, K. et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108, 17–29 (2002). This work establishes the temporal coordination between OSX and RUNX2 activation for osteoblast differentiation.CAS 
PubMed 

Google Scholar 
69.Yang, X. & Karsenty, G. Transcription factors in bone: developmental and pathological aspects. Trends Mol. Med. 8, 340–345 (2002).CAS 
PubMed 

Google Scholar 
70.Zhou, X. et al. Multiple functions of osterix are required for bone growth and homeostasis in postnatal mice. Proc. Natl Acad. Sci. USA 107, 12919–12924 (2010).CAS 
PubMed 

Google Scholar 
71.Liu, T. M. & Lee, E. H. Transcriptional regulatory cascades in Runx2-dependent bone development. Tissue Eng. Part B Rev. 19, 254–263 (2013).PubMed 

Google Scholar 
72.St-Arnaud, R. & Hekmatnejad, B. Combinatorial control of ATF4-dependent gene transcription in osteoblasts. Ann. N. Y. Acad. Sci. 1237, 11–18 (2011).CAS 
PubMed 

Google Scholar 
73.Yang, X. et al. ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology: implication for Coffin-Lowry syndrome. Cell 117, 387–398 (2004).CAS 
PubMed 

Google Scholar 
74.Jing, D. et al. The role of microRNAs in bone remodeling. Int. J. Oral. Sci. 7, 131–143 (2015).CAS 
PubMed 
PubMed Central 

Google Scholar 
75.Xiao, G. et al. Cooperative interactions between activating transcription factor 4 and Runx2/Cbfa1 stimulate osteoblast-specific osteocalcin gene expression. J. Biol. Chem. 280, 30689–30696 (2005).CAS 
PubMed 

Google Scholar 
76.Wagner, E. F. Functions of AP1 (Fos/Jun) in bone development. Ann. Rheum. Dis. 61, ii40–ii42 (2002).CAS 
PubMed 
PubMed Central 

Google Scholar 
77.Kenner, L. et al. Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects. J. Cell Biol. 164, 613–623 (2004).CAS 
PubMed 
PubMed Central 

Google Scholar 
78.Zambotti, A., Makhluf, H., Shen, J. & Ducy, P. Characterization of an osteoblast-specific enhancer element in the CBFA1. Gene 277, 41497–41506 (2002).CAS 

Google Scholar 
79.Jochum, W. et al. Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1. Nat. Med. 6, 980–984 (2000).CAS 
PubMed 

Google Scholar 
80.Bozec, A. et al. Fra-2/AP-1 controls bone formation by regulating osteoblast differentiation and collagen production. J. Cell Biol. 190, 1093–1106 (2010).CAS 
PubMed 
PubMed Central 

Google Scholar 
81.Nüsslein-volhard, C. & Wieschaus, E. Mutations affecting segment number and polarity in drosophila. Nature. 287, 795–801 (1980).PubMed 

Google Scholar 
82.McMahon, A. P., Ingham, P. W. & Tabin, C. J. 1 Developmental roles and clinical significance of Hedgehog signaling. Curr. Top. Dev. Biol. 53, 1–114 (2003).CAS 
PubMed 

Google Scholar 
83.Ocbina, P. J. R. & Anderson, K. V. Intraflagellar transport, Cilia, and mammalian hedgehog signaling: analysis in mouse embryonic fibroblasts. Dev. Dyn. 237, 2030–2038 (2008).PubMed 
PubMed Central 

Google Scholar 
84.Riddle, R. D., Johnson, R. L., Laufer, E. & Tabin, C. Sonic hedgehog mediates the polarizing activity of the ZPA. Cell 75, 1401–1416 (1993).CAS 
PubMed 

Google Scholar 
85.Rohatgi, R., Milenkovic, L. & Scott, M. P. Patched1 regulates hedgehog signaling at the primary cilium. Science. 317, 372–376 (2007).CAS 
PubMed 

Google Scholar 
86.Corbit, K. C. et al. Vertebrate Smoothened functions at the primary cilium. Nature. 437, 1018–1021 (2005).CAS 
PubMed 

Google Scholar 
87.Towers, M., Mahood, R., Yin, Y. & Tickle, C. Integration of growth and specification in chick wing digit-patterning. Nature 452, 882–886 (2008).CAS 
PubMed 

Google Scholar 
88.Chinnaiya, K., Tickle, C. & Towers, M. Sonic hedgehog-expressing cells in the developing limb measure time by an intrinsic cell cycle clock. Nat. Commun. 5, 4230 (2014).CAS 
PubMed 
PubMed Central 

Google Scholar 
89.Wang, B., Fallon, J. F. & Beachy, P. A. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Cell 100, 423–434 (2000).CAS 
PubMed 

Google Scholar 
90.Mo, R. et al. Specific and redundant functions of Gli2 and Gli3 zinc finger genes in skeletal patterning and development. Development 124, 113–123 (1997).CAS 
PubMed 

Google Scholar 
91.Park, H. et al. Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation. Development 127, 1593–1605 (2000).CAS 
PubMed 

Google Scholar 
92.Hojo, H. et al. Gli1 protein participates in hedgehog-mediated specification of osteoblast lineage during endochondral ossification. J. Biol. Chem. 287, 17860–17869 (2012).CAS 
PubMed 
PubMed Central 

Google Scholar 
93.Amano, K., Densmore, M., Nishimura, R. & Lanske, B. Indian hedgehog signaling regulates transcription and expression of collagen type X via Runx2/Smads interactions. J. Biol. Chem. 289, 24898–24910 (2014).CAS 
PubMed 
PubMed Central 

Google Scholar 
94.Jemtland, R., Divieti, P., Lee, K. & Segre, G. V. Hedgehog promotes primary osteoblast differentiation and increases PTHrP mRNA expression and iPTHrP secretion. Bone 32, 611–620 (2003).CAS 
PubMed 

Google Scholar 
95.Long, F. & Linsenmayer, T. F. Regulation of growth region cartilage proliferation and differentiation by perichondrium. Development 125, 1067–1073 (1998).CAS 
PubMed 

Google Scholar 
96.Mak, K. K., Chen, M. H., Day, T. F., Chuang, P. T. & Yang, Y. Wnt/β-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation. Development 133, 3695–3707 (2006).CAS 
PubMed 

Google Scholar 
97.Day, T. F. & Yang, Y. Wnt and hedgehog signaling pathways in bone development. J. Bone Joint Surg. Ser. Am. 90, 19–24 (2008).
Google Scholar 
98.Hojo, H. et al. Hedgehog-Gli activators direct osteo-chondrogenic function of bone morphogenetic protein toward osteogenesis in the perichondrium. J. Biol. Chem. 288, 9924–9932 (2013).CAS 
PubMed 
PubMed Central 

Google Scholar 
99.Schroeter, E. H., Kisslinger, J. A. & Kopan, R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 393, 382–386 (1998).CAS 
PubMed 

Google Scholar 
100.Zanotti, S. & Canalis, E. Notch signaling and the skeleton. Endocr. Rev. 37, 223–253 (2016).CAS 
PubMed 
PubMed Central 

Google Scholar 
101.Tu, X. et al. Physiological Notch signaling maintains bone homeostasis via RBPjk and Hey upstream of NFATc1. PLoS Genet. 8, e1002577 (2012).CAS 
PubMed 
PubMed Central 

Google Scholar 
102.Hilton, M. J. et al. Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat. Med. 14, 306–314 (2008).CAS 
PubMed 
PubMed Central 

Google Scholar 
103.Engin, F. et al. Dimorphic effects of Notch signaling in bone homeostasis. Nat. Med. 14, 299–305 (2008).CAS 
PubMed 
PubMed Central 

Google Scholar 
104.Canalis, E., Parker, K., Feng, J. Q. & Zanotti, S. Osteoblast lineage-specific effects of notch activation in the skeleton. Endocrinology 154, 623–634 (2013).CAS 
PubMed 

Google Scholar 
105.Zanotti, S. & Canalis, E. Notch1 and Notch2 expression in osteoblast precursors regulates femoral microarchitecture. Bone 62, 22–28 (2014).CAS 
PubMed 
PubMed Central 

Google Scholar 
106.Kim, J. B. et al. Bone regeneration is regulated by Wnt signaling. J. Bone Miner. Res. 22, 1913–1923 (2007).CAS 
PubMed 

Google Scholar 
107.Huelsken, J. & Birchmeier, W. New aspects of Wnt signaling pathways in higher vertebrates. Curr. Opin. Genet. Dev. 11, 547–553 (2001).CAS 
PubMed 

Google Scholar 
108.Williams, B. O. & Insogna, K. L. Where Wnts went: the exploding field of Lrp5 and Lrp6 signaling in bone. J. Bone Miner. Res. 24, 171–178 (2009).CAS 
PubMed 

Google Scholar 
109.Joiner, D. M., Ke, J., Zhong, Z., Xu, H. E. & Williams, B. O. LRP5 and LRP6 in development and disease. Trends Endocrinol. Metab. 24, 31–39 (2013).CAS 
PubMed 
PubMed Central 

Google Scholar 
110.Baron, R. & Kneissel, M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat. Med. 19, 179–192 (2013).CAS 
PubMed 

Google Scholar 
111.Boyden, L. M. et al. High bone density due to a mutation in LDL-receptor-related protein 5. N. Engl. J. Med. 346, 1513–1521 (2002).CAS 
PubMed 

Google Scholar 
112.Little, R. D. et al. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am. J. Hum. Genet. 70, 11–19 (2002).CAS 
PubMed 

Google Scholar 
113.Houschyar, K. S. et al. Wnt pathway in bone repair and regeneration – what do we know so far. Front. Cell Dev. Biol. 6, 170 (2019).PubMed 
PubMed Central 

Google Scholar 
114.Minear, S. et al. Wnt proteins promote bone regeneration. Sci. Transl Med. 2, 29ra30 (2010).PubMed 

Google Scholar 
115.Poole, K. E. S. et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J. 19, 1842–1844 (2005).CAS 
PubMed 

Google Scholar 
116.Ai, M., Holmen, S. L., Van Hul, W., Williams, B. O. & Warman, M. L. Reduced affinity to and inhibition by DKK1 form a common mechanism by which high bone mass-associated missense mutations in LRP5 affect canonical Wnt signaling. Mol. Cell Biol. 25, 4946–4955 (2005).CAS 
PubMed 
PubMed Central 

Google Scholar 
117.Brunkow, M. E. et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am. J. Hum. Genet. 68, 577–589 (2001).CAS 
PubMed 
PubMed Central 

Google Scholar 
118.Holmen, S. L. et al. Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. J. Bone Miner. Res. 19, 2033–2040 (2004).CAS 
PubMed 

Google Scholar 
119.Kubota, T. et al. Lrp6 hypomorphic mutation affects bone mass through bone resorption in mice and impairs interaction with Mesd. J. Bone Miner. Res. 23, 1661–1671 (2008).CAS 
PubMed 

Google Scholar 
120.Lin, G. L. & Hankenson, K. D. Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation. J. Cell Biochem. 112, 3491–3501 (2011).CAS 
PubMed 
PubMed Central 

Google Scholar 
121.Wu, M., Chen, G. & Li, Y. P. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res. 4, 16009 (2016).PubMed 
PubMed Central 

Google Scholar 
122.Itasaki, N. & Hoppler, S. Crosstalk between Wnt and bone morphogenic protein signaling: a turbulent relationship. Dev. Dyn. 239, 16–33 (2010).CAS 
PubMed 

Google Scholar 
123.Luo, Q. et al. Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells. J. Biol. Chem. 279, 55958–55968 (2004).CAS 
PubMed 

Google Scholar 
124.Si, W. et al. CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells. Mol. Cell Biol. 26, 2955–2964 (2006).CAS 
PubMed 
PubMed Central 

Google Scholar 
125.Boland, G. M., Perkins, G., Hall, D. J. & Tuan, R. S. Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J. Cell Biochem. 93, 1210–1230 (2004).CAS 
PubMed 

Google Scholar 
126.Chen, Y. et al. β-Catenin signaling pathway is crucial for bone morphogenetic protein 2 to induce new bone formation. J. Biol. Chem. 282, 526–533 (2007).CAS 
PubMed 

Google Scholar 
127.Zhang, M. et al. BMP-2 modulates β-catenin signaling through stimulation of Lrp5 expression and inhibition of β-TrCP expression in osteoblasts. J. Cell Biochem. 108, 896–905 (2009).CAS 
PubMed 
PubMed Central 

Google Scholar 
128.Wrana, J. L. et al. TGFβ signals through a heteromeric protein kinase receptor complex. Cell 71, 1003–1014 (1992).CAS 
PubMed 

Google Scholar 
129.Schmierer, B. & Hill, C. S. TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat. Rev. Mol. Cell Biol. 8, 970–982 (2007).CAS 
PubMed 

Google Scholar 
130.Salazar, V. S., Gamer, L. W. & Rosen, V. BMP signalling in skeletal development, disease and repair. Nat. Rev. Endocrinol. 12, 203–221 (2016).CAS 
PubMed 

Google Scholar 
131.Katagiri, T. & Watabe, T. Bone morphogenetic proteins. Cold Spring Harb Perspect. Biol. https://doi.org/10.1101/cshperspect.a021899 (2016).PubMed 
PubMed Central 

Google Scholar 
132.Salazar, V. S. et al. Reactivation of a developmental Bmp2 signaling center is required for therapeutic control of the murine periosteal niche. eLife https://doi.org/10.7554/eLife.42386 (2019).PubMed 
PubMed Central 

Google Scholar 
133.Bandyopadhyay, A. et al. Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis. PLoS Genet. 2, 2116–2130 (2006).CAS 

Google Scholar 
134.Tsuji, K. et al. BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat. Genet. 38, 1424–1429 (2006). This work demonstrates the role of reoccurring BMP signalling for limb development and fracture healing of the limb.CAS 
PubMed 

Google Scholar 
135.Lim, J. et al. Dual function of Bmpr1a signaling in restricting preosteoblast proliferation and stimulating osteoblast activity in mouse. Development 143, 339–347 (2016).CAS 
PubMed 
PubMed Central 

Google Scholar 
136.Fujii, M. et al. Roles of bone morphogenetic protein type I receptors and Smad proteins in osteoblast and chondroblast differentiation. Mol. Biol. Cell 10, 3801–3813 (1999).CAS 
PubMed 
PubMed Central 

Google Scholar 
137.Singhatanadgit, W. & Olsen, I. Endogenous BMPR-IB signaling is required for early osteoblast differentiation of human bone cells. Vitr. Cell Dev. Biol. Anim. 47, 251–259 (2011).CAS 

Google Scholar 
138.Yoshida, Y. et al. Negative regulation of BMP/Smad signaling by Tob in osteoblasts. Cell 103, 1085–1097 (2000).CAS 
PubMed 

Google Scholar 
139.Zhang, Y. et al. Loss of BMP signaling through BMPR1A in osteoblasts leads to greater collagen cross-link maturation and material-level mechanical properties in mouse femoral trabecular compartments. Bone 88, 74–84 (2016).CAS 
PubMed 
PubMed Central 

Google Scholar 
140.Johnson, D. E. & Williams, L. T. Structural and functional diversity in the FGF receptor multigene family. Adv. Cancer Res. 60, 1–41 (1992).
Google Scholar 
141.Ornitz, D. M. et al. Receptor specificity of the fibroblast growth factor family. J. Biol. Chem. 271, 15292–15297 (1996).CAS 
PubMed 

Google Scholar 
142.Ornitz, D. M. FGF signaling in the developing endochondral skeleton. Cytokine Growth Factor. Rev. 16, 205–213 (2005).CAS 
PubMed 
PubMed Central 

Google Scholar 
143.Montero, A. et al. Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation. J. Clin. Invest. 105, 1085–1093 (2000).CAS 
PubMed 
PubMed Central 

Google Scholar 
144.Zhou, M. et al. Fibroblast growth factor 2 control of vascular tone. Nat. Med. 4, 201–207 (1998).CAS 
PubMed 
PubMed Central 

Google Scholar 
145.Crossley, P. H., Minowada, G., MacArthur, C. A. & Martin, G. R. Roles for FGF8 in the induction, initiation, and maintenance of chick limb development. Cell 84, 127–136 (1996).CAS 
PubMed 

Google Scholar 
146.Lewandoski, M., Sun, X. & Martin, G. R. Fgf8 signalling from the AER is essential for normal limb development. Nat. Genet. 26, 460–463 (2000).CAS 
PubMed 

Google Scholar 
147.Martin, G. R. The roles of FGFs in the early development of vertebrate limbs. Genes Dev. 12, 1571–1586 (1998).CAS 
PubMed 

Google Scholar 
148.Min, H. et al. Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless. Genes Dev. 12, 3156–3161 (1998).CAS 
PubMed 
PubMed Central 

Google Scholar 
149.Ohuchi, H. et al. The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor. Development 124, 2235–2244 (1997).CAS 
PubMed 

Google Scholar 
150.Mahmood, R. et al. A role for FGF-8 in the initiation and maintenance of vertebrate limb bud outgrowth. Curr. Biol. 5, 797–806 (1995).CAS 
PubMed 

Google Scholar 
151.Heikinheimo, M., Lawshé, A., Shackleford, G. M., Wilson, D. B. & MacArthur, C. A. Fgf-8 expression in the post-gastrulation mouse suggests roles in the development of the face, limbs and central nervous system. Mech. Dev. 48, 129–138 (1994).CAS 
PubMed 

Google Scholar 
152.Lin, J. M. et al. Actions of fibroblast growth factor-8 in bone cells in vitro. Am. J. Physiol. Endocrinol. Metab. 297, E142–E150 (2009).CAS 
PubMed 

Google Scholar 
153.Yamaguchi, T. P., Conlon, R. A. & Rossant, J. Expression of the fibroblast growth factor receptor FGFR-1/flg during gastrulation and segmentation in the mouse embryo. Dev. Biol. 152, 75–88 (1992).CAS 
PubMed 

Google Scholar 
154.Deng, C. et al. Fibroblast growth factor receptor-1 (FGFR-1) is essential for normal neural tube and limb development. Dev. Biol. 185, 42–54 (1997).CAS 
PubMed 

Google Scholar 
155.Jacob, A. L., Smith, C., Partanen, J. & Ornitz, D. M. Fibroblast growth factor receptor 1 signaling in the osteo-chondrogenic cell lineage regulates sequential steps of osteoblast maturation. Dev. Biol. 296, 315–328 (2006).CAS 
PubMed 
PubMed Central 

Google Scholar 
156.Verheyden, J. M., Lewandoski, M., Deng, C., Harfe, B. D. & Sun, X. Conditional inactivation of Fgfr1 in mouse defines its role in limb bud establishment, outgrowth and digit patterning. Development 132, 4235–4245 (2005).CAS 
PubMed 
PubMed Central 

Google Scholar 
157.Orr-Urtreger, A. et al. Developmental localization of the splicing alternatives of fibroblast growth factor receptor-2 (FGFR2). Dev. Biol. 158, 475–486 (1993).CAS 
PubMed 

Google Scholar 
158.Li, X. et al. Fibroblast growth factor signaling and basement membrane assembly are connected during epithelial morphogenesis of the embryoid body. J. Cell Biol. 153, 811–822 (2001).CAS 
PubMed 
PubMed Central 

Google Scholar 
159.Arman, E., Haffner-Krausz, R., Chen, Y., Heath, J. K. & Lonai, P. Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development. Proc. Natl Acad. Sci. USA 95, 5082–5087 (1998).CAS 
PubMed 

Google Scholar 
160.Xu, X. et al. Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development 125, 753–765 (1998).CAS 
PubMed 

Google Scholar 
161.Wang, Y. et al. Abnormalities in cartilage and bone development in the Apert syndrome FGFR2(+/S252W) mouse. Development 132, 3537–3548 (2005).CAS 
PubMed 
PubMed Central 

Google Scholar 
162.Claes, L., Recknagel, S. & Ignatius, A. Fracture healing under healthy and inflammatory conditions. Nat. Rev. Rheumatol. 8, 133–143 (2012).CAS 
PubMed 

Google Scholar 
163.Glynne, A. J., Andrew, S. M., Freemont, A. J. & Marsh, D. R. Inflammatory cells in normal human fracture healing. Acta Orthop. 65, 462–466 (1994).
Google Scholar 
164.Bolander, M. E. Regulation of fracture repair by growth factors. Exp. Biol. Med. 200, 165–170 (1992).CAS 

Google Scholar 
165.Croes, M. et al. Proinflammatory mediators enhance the osteogenesis of human mesenchymal stem cells after lineage commitment. PLoS ONE 10, e0132781 (2015).PubMed 
PubMed Central 

Google Scholar 
166.Lu, L. Y. et al. Pro-inflammatory M1 macrophages promote Osteogenesis by mesenchymal stem cells via the COX-2-prostaglandin E2 pathway. J. Orthop. Res. 35, 2378–2385 (2017).CAS 
PubMed 
PubMed Central 

Google Scholar 
167.Bernhardsson, M. & Aspenberg, P. Osteoblast precursors and inflammatory cells arrive simultaneously to sites of a trabecular-bone injury. Acta Orthop. 89, 457–461 (2018).PubMed 
PubMed Central 

Google Scholar 
168.Ono, T. et al. IL-17-producing γδT cells enhance bone regeneration. Nat. Commun. 7, 10928 (2016). This work shows that the presence of the proinflammatory cytokine IL-17, from the niche, aided in bone regrowth after injury.CAS 
PubMed 
PubMed Central 

Google Scholar 
169.Goerke, S. M., Obermeyer, J., Plaha, J., Stark, G. B. & Finkenzeller, G. Endothelial progenitor cells from peripheral blood support bone regeneration by provoking an angiogenic response. Microvasc. Res. 98, 40–47 (2015).CAS 
PubMed 

Google Scholar 
170.Langen, U. H. et al. Cell-matrix signals specify bone endothelial cells during developmental osteogenesis. Nat. Cell Biol. 19, 189–201 (2017).CAS 
PubMed 
PubMed Central 

Google Scholar 
171.Kusumbe, A. P., Ramasamy, S. K. & Adams, R. H. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 507, 323–328 (2014).CAS 
PubMed 
PubMed Central 

Google Scholar 
172.Ramasamy, S. K., Kusumbe, A. P., Wang, L. & Adams, R. H. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Nature. 507, 376–380 (2014).CAS 
PubMed 
PubMed Central 

Google Scholar 
173.Cao, J. et al. Sensory nerves affect bone regeneration in rabbit mandibular distraction osteogenesis. Int. J. Med. Sci. 16, 831–837 (2019).CAS 
PubMed 
PubMed Central 

Google Scholar 
174.Jones, R. E. et al. Skeletal stem cell-Schwann cell circuitry in Mandibular repair. Cell Rep. 28, 2757–2766.e5 (2019).CAS 
PubMed 
PubMed Central 

Google Scholar 
175.Park, B. W., Kim, J. R., Lee, J. H. & Byun, J. H. Expression of nerve growth factor and vascular endothelial growth factor in the inferior alveolar nerve after distraction osteogenesis. Int. J. Oral Maxillofac. Surg. 35, 624–630 (2006).PubMed 

Google Scholar 
176.Wang, L. et al. Locally applied nerve growth factor enhances bone consolidation in a rabbit model of mandibular distraction osteogenesis. J. Orthop. Res. 24, 2238–2245 (2006).CAS 
PubMed 

Google Scholar 
177.Emara, K. M., Diab, R. A. & Emara, A. K. Recent biological trends in management of fracture non-union. World J. Orthop. 6, 623–628 (2015).PubMed 
PubMed Central 

Google Scholar 
178.Panteli, M., Pountos, I., Jones, E. & Giannoudis, P. V. Biological and molecular profile of fracture non-union tissue: current insights. J. Cell Mol. Med. 19, 685–713 (2015).PubMed 
PubMed Central 

Google Scholar 
179.Jones, A. L. et al. Recombinant human BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects: a randomized, controlled trial. J. Bone Joint Surg. Ser. Am. 88, 1431–1441 (2006).
Google Scholar 
180.Kawaguchi, H. et al. Local application of recombinant human fibroblast growth factor-2 on bone repair: a dose-escalation prospective trial on patients with osteotomy. J. Orthop. Res. 25, 480–487 (2007).CAS 

Google Scholar 
181.Babcock, S. & Kellam, J. F. Hip fracture nonunions: diagnosis, treatment, and special considerations in elderly patients. Adv. Orthop. https://doi.org/10.1155/2018/1912762 (2018).PubMed 
PubMed Central 

Google Scholar 
182.Atanelov, Z. & Bentley, T. P. Greenstick fracture. StatPearls (2018).183.Kraft, C. T. et al. Trauma-induced heterotopic bone formation and the role of the immune system: a review. J. Trauma. Acute Care Surg. 80, 156–165 (2016).CAS 
PubMed 
PubMed Central 

Google Scholar 
184.Huang, H. et al. Relationship between heterotopic ossification and traumatic brain injury: Why severe traumatic brain injury increases the risk of heterotopic ossification. J. Orthop. Transl 12, 16–25 (2018).
Google Scholar 
185.Sorkin, M. et al. Regulation of heterotopic ossification by monocytes in a mouse model of aberrant wound healing. Nat Commun. https://doi.org/10.1038/s41467-019-14172-4 (2020).This work determines CD47 activation as a therapeutic approach for heterotopic ossification formation during wound healing.186.Agarwal, S. et al. Disruption of neutrophil extracellular traps (NETs) links mechanical strain to post-traumatic inflammation. Front. Immunol. 10, 2148 (2019).CAS 
PubMed 
PubMed Central 

Google Scholar 
187.Torossian, F. et al. Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications. JCI Insight 2, e96034 (2017).PubMed Central 

Google Scholar 
188.Hwang, C. et al. Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification. Bone Res. 7, 36 (2019).CAS 
PubMed 
PubMed Central 

Google Scholar 
189.Hsieh, H. H. S. et al. Coordinating tissue regeneration through transforming growth factor-β activated kinase 1 inactivation and reactivation. Stem Cells 37, 766–778 (2019).CAS 
PubMed 
PubMed Central 

Google Scholar 
190.Raggatt, L. J. et al. Fracture healing via periosteal callus formation requires macrophages for both initiation and progression of early endochondral ossification. Am. J. Pathol. 184, 3192–3204 (2014).CAS 
PubMed 

Google Scholar 
191.Agarwal, S. et al. Inhibition of Hif1α prevents both trauma-induced and genetic heterotopic ossification. Proc. Natl Acad. Sci. USA 113, E338–E347 (2016).CAS 
PubMed 

Google Scholar 
192.Agarwal, S. et al. Scleraxis-lineage cells contribute to ectopic bone formation in muscle and tendon. Stem Cells 35, 705–710 (2017).CAS 
PubMed 

Google Scholar 
193.Loder, S. J. et al. Characterizing the circulating cell populations in traumatic heterotopic ossification. Am. J. Pathol. 188, 2464–2473 (2018).CAS 
PubMed 
PubMed Central 

Google Scholar 
194.Dey, D. et al. Two tissue-resident progenitor lineages drive distinct phenotypes of heterotopic ossification. Sci. Transl Med. https://doi.org/10.1126/scitranslmed.aaf1090 (2016).PubMed 
PubMed Central 

Google Scholar 
195.Kan, C. et al. Gli1-labeled adult mesenchymal stem/progenitor cells and hedgehog signaling contribute to endochondral heterotopic ossification. Bone 109, 71–79 (2018).CAS 
PubMed 

Google Scholar 
196.Eisner, C. et al. Murine tissue-resident PDGFRα+ fibro-adipogenic progenitors spontaneously acquire osteogenic phenotype in an altered inflammatory environment. J. Bone Miner. Res. (2020).197.Agarwal, S. et al. Analysis of bone-cartilage-stromal progenitor populations in trauma induced and genetic models of heterotopic ossification. Stem Cells 34, 1692–1701 (2016).CAS 
PubMed 
PubMed Central 

Google Scholar 
198.Agarwal, S. et al. Strategic targeting of multiple BMP receptors prevents trauma-induced heterotopic ossification. Mol. Ther. 25, 1974–1987 (2017).CAS 
PubMed 
PubMed Central 

Google Scholar 
199.Huber, A. K. et al. Immobilization after injury alters extracellular matrix and stem cell fate. J. Clin. Invest. https://doi.org/10.1172/JCI136142 (2020).PubMed 

Google Scholar 
200.Stepien, D. M. et al. Tuning macrophage phenotype to mitigate skeletal muscle fibrosis. J. Immunol. 204, 2203–2215 (2020).CAS 
PubMed 

Google Scholar 
201.Peterson, J. R. et al. Effects of aging on osteogenic response and heterotopic ossification following burn injury in mice. Stem Cell Dev. 24, 205–213 (2015).CAS 

Google Scholar 
202.Ranganathan, K. et al. Role of gender in burn-induced heterotopic ossification and mesenchymal cell osteogenic differentiation. Plast. Reconstr. Surg. 135, 1631–1641 (2015).CAS 
PubMed 
PubMed Central 

Google Scholar 
203.Akiyama, H. et al. Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors. Proc. Natl Acad. Sci. USA 102, 14665–14670 (2005).CAS 
PubMed 

Google Scholar 
204.Maes, C. et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev. Cell 19, 329–344 (2010).CAS 
PubMed 
PubMed Central 

Google Scholar 
205.Greenbaum, A. et al. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature. 495, 227–230 (2013).CAS 
PubMed 
PubMed Central 

Google Scholar 
206.Xiong, J. et al. Osteocytes, not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling bone. PLoS ONE https://doi.org/10.1371/journal.pone.0138189 (2015).207.Pineault, K. M. et al. Hox11 genes regulate postnatal longitudinal bone growth and growth plate proliferation. Biol. Open 4, 1538–1548 (2015).CAS 
PubMed 
PubMed Central 

Google Scholar 
208.Yu, V. W. C. et al. FIAT represses ATF4-mediated transcription to regulate bone mass in transgenic mice. J. Cell Biol. 169, 591–601 (2005).CAS 
PubMed 
PubMed Central 

Google Scholar 
209.Ambrogini, E. et al. FoxO-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice. Cell Metab. 11, 136–146 (2010).CAS 
PubMed 
PubMed Central 

Google Scholar 
210.Shimoyama, A. et al. Ihh/Gli2 signaling promotes osteoblast differentiation by regulating Runx2 expression and function. Mol. Biol. Cell 18, 2411–2418 (2007).CAS 
PubMed 
PubMed Central 

Google Scholar 
211.Li, J. et al. Suppressor of fused restraint of hedgehog activity level is critical for osteogenic proliferation and differentiation during calvarial bone development. J. Biol. Chem. 292, 15814–15825 (2017).CAS 
PubMed 
PubMed Central 

Google Scholar 
212.Funato, N. et al. Hand2 controls osteoblast differentiation in the branchial arch by inhibiting DNA binding of Runx2. Development 136, 615–625 (2009).CAS 
PubMed 

Google Scholar 
213.Kanzler, B., Kuschert, S. J., Liu, Y. H. & Mallo, M. Hoxa-2 restricts the chondrogenic domain and inhibits bone formation during development of the branchial area. Development 125, 2587–2597 (1998).CAS 
PubMed 

Google Scholar 
214.Komori, T. Regulation of osteoblast differentiation by runx2. Adv. Exp. Med. Biol. 658, 43–49 (2010).CAS 
PubMed 

Google Scholar 
215.Hong, J. H. et al. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science 309, 1074–1078 (2005).CAS 
PubMed 

Google Scholar 
216.Bialek, P. et al. A twist code determines the onset of osteoblast differentiation. Dev. Cell 6, 423–435 (2004).CAS 
PubMed 

Google Scholar 
217.Cancela, L., Hsieh, C. L. & Francke, U. P. P. Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene. J. Biol. Chem. 265, 15040–15048 (1990).CAS 
PubMed 

Google Scholar 
218.Karsenty, G. & Park, R. W. Regulation of type I collagen genes expression. Int. Rev. Immunol. 12, 177–185 (1995).CAS 
PubMed 

Google Scholar 
219.Pinzone, J. J. et al. The role of Dickkopf-1 in bone development, homeostasis, and disease. Blood 113, 517–525 (2009).CAS 
PubMed 
PubMed Central 

Google Scholar 
220.Kim, J. B. et al. Reconciling the roles of FAK in osteoblast differentiation, osteoclast remodeling, and bone regeneration. Bone 41, 39–51 (2007).CAS 
PubMed 
PubMed Central 

Google Scholar 
221.Li, X. et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J. Biol. Chem. 280, 19883–19887 (2005).CAS 
PubMed 

Google Scholar 

Read More

Show More

Related Articles

Leave a Reply

Your email address will not be published.

Back to top button
Close
Close