Yin T, Li L. The stem cell niches in bone. J Clin Investig. 2006;116:1195–201.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Salhotra A, Shah HN, Levi B, Longaker MT. Mechanisms of bone development and repair. Nat Rev Mol Cell Biol. 2020;21:696–711.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Tang Y, Wu X, Lei W, Pang L, Wan C, Shi Z, Zhao L, Nagy TR, Peng X, Hu J, et al. TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med. 2009;15:757–65.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 1998;95:3597–602.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Xiong J, Piemontese M, Onal M, Campbell J, Goellner JJ, Dusevich V, Bonewald L, Manolagas SC, O’Brien CA. Osteocytes, not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling bone. PLoS ONE. 2015;10: e0138189.

Article  PubMed Central  PubMed  Google Scholar 

Lerner UH, Kindstedt E, Lundberg P. The critical interplay between bone resorbing and bone forming cells. J Clin Periodontol. 2019;46(Suppl 21):33–51.

Article  PubMed  Google Scholar 

Zuo C, Huang Y, Bajis R, Sahih M, Li YP, Dai K, Zhang X. Osteoblastogenesis regulation signals in bone remodeling. Osteoporos Int. 2012;23:1653–63.

Article  CAS  PubMed  Google Scholar 

Chang H, Brown CW, Matzuk MM. Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr Rev. 2002;23:787–823.

Article  CAS  PubMed  Google Scholar 

Hering S, Isken E, Knabbe C, Janott J, Jost C, Pommer A, Muhr G, Schatz H, Pfeiffer AF. TGFbeta1 and TGFbeta2 mRNA and protein expression in human bone samples. Exp Clin Endocrinol Diabetes. 2001;109:217–26.

Article  CAS  PubMed  Google Scholar 

Seyedin SM, Thomas TC, Thompson AY, Rosen DM, Piez KA. Purification and characterization of two cartilage-inducing factors from bovine demineralized bone. Proc Natl Acad Sci USA. 1985;82:2267–71.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003;425:577–84.

Article  CAS  PubMed  Google Scholar 

Reddi AH. Role of morphogenetic proteins in skeletal tissue engineering and regeneration. Nat Biotechnol. 1998;16:247–52.

Article  CAS  PubMed  Google Scholar 

Wu M, Chen G, Li YP. TGF-beta and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res. 2016;4:16009.

Article  PubMed Central  PubMed  Google Scholar 

Walsh DW, Godson C, Brazil DP, Martin F. Extracellular BMP-antagonist regulation in development and disease: tied up in knots. Trends Cell Biol. 2010;20:244–56.

Article  CAS  PubMed  Google Scholar 

Avsian-Kretchmer O, Hsueh AJ. Comparative genomic analysis of the eight-membered ring cystine knot-containing bone morphogenetic protein antagonists. Mol Endocrinol. 2004;18:1–12.

Article  CAS  PubMed  Google Scholar 

Todd GM, Gao Z, Hyvonen M, Brazil DP, Ten Dijke P. Secreted BMP antagonists and their role in cancer and bone metastases. Bone. 2020;137: 115455.

Article  CAS  PubMed  Google Scholar 

Canalis E, Economides AN, Gazzerro E. Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev. 2003;24:218–35.

Article  CAS  PubMed  Google Scholar 

Chang C. Agonists and antagonists of TGF-beta family ligands. Cold Spring Harb Perspect Biol. 2016;8:a021923.

Article  PubMed Central  PubMed  Google Scholar 

Wu FJ, Lin TY, Sung LY, Chang WF, Wu PC, Luo CW. BMP8A sustains spermatogenesis by activating both SMAD1/5/8 and SMAD2/3 in spermatogonia. Sci Signal. 2017;10:eaal1910.

Article  PubMed  Google Scholar 

Amend SR, Valkenburg KC, Pienta KJ. Murine hind limb long bone dissection and bone marrow isolation. J Vis Exp. 2016;14:e53936.

Google Scholar 

Regier N, Frey B. Experimental comparison of relative RT-qPCR quantification approaches for gene expression studies in poplar. BMC Mol Biol. 2010;11:57.

Article  PubMed Central  PubMed  Google Scholar 

Mazerbourg S, Sangkuhl K, Luo CW, Sudo S, Klein C, Hsueh AJ. Identification of receptors and signaling pathways for orphan bone morphogenetic protein/growth differentiation factor ligands based on genomic analyses. J Biol Chem. 2005;280:32122–32.

Article  CAS  PubMed  Google Scholar 

Zhao S, Ye Z, Stanton R. Misuse of RPKM or TPM normalization when comparing across samples and sequencing protocols. RNA. 2020;26:903–9.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Zwiener I, Frisch B, Binder H. Transforming RNA-Seq data to improve the performance of prognostic gene signatures. PLoS ONE. 2014;9: e85150.

Article  PubMed Central  PubMed  Google Scholar 

Gazzerro E, Gangji V, Canalis E. Bone morphogenetic proteins induce the expression of noggin, which limits their activity in cultured rat osteoblasts. J Clin Investig. 1998;102:2106–14.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet. 2011;377:1276–87.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Benisch P, Schilling T, Klein-Hitpass L, Frey SP, Seefried L, Raaijmakers N, Krug M, Regensburger M, Zeck S, Schinke T, et al. The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors. PLoS ONE. 2012;7: e45142.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Solloway MJ, Dudley AT, Bikoff EK, Lyons KM, Hogan BL, Robertson EJ. Mice lacking Bmp6 function. Dev Genet. 1998;22:321–39.

Article  CAS  PubMed  Google Scholar 

Tsuji K, Cox K, Bandyopadhyay A, Harfe BD, Tabin CJ, Rosen V. BMP4 is dispensable for skeletogenesis and fracture-healing in the limb. J Bone Joint Surg Am. 2008;90(Suppl 1):14–8.

Article  PubMed  Google Scholar 

Tsuji K, Bandyopadhyay A, Harfe BD, Cox K, Kakar S, Gerstenfeld L, Einhorn T, Tabin CJ, Rosen V. BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat Genet. 2006;38:1424–9.

Article  CAS  PubMed  Google Scholar 

Bandyopadhyay A, Tsuji K, Cox K, Harfe BD, Rosen V, Tabin CJ. Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis. PLoS Genet. 2006;2: e216.

Article  PubMed Central  PubMed  Google Scholar 

Wu FJ, Wang YW, Luo CW. Human bone morphogenetic protein 8A promotes expansion and prevents apoptosis of cumulus cells in vitro. Mol Cell Endocrinol. 2020;522: 111121.

Article  PubMed  Google Scholar 

Wu FJ, Wang YW, Luo CW. Human BMP8A suppresses luteinization of rat granulosa cells via the SMAD1/5/8 pathway. Reproduction. 2020;159:315–24.

Article  CAS  PubMed  Google Scholar 

DiLeone RJ, King JA, Storm EE, Copeland NG, Jenkins NA, Kingsley DM. The Bmp8 gene is expressed in developing skeletal tissue and maps near the Achondroplasia locus on mouse chromosome 4. Genomics. 1997;40:196–8.

Article  CAS  PubMed  Google Scholar 

Cho TJ, Gerstenfeld LC, Einhorn TA. Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing. J Bone Miner Res. 2002;17:513–20.

Article  CAS  PubMed  Google Scholar 

Yu YY, Lieu S, Lu C, Miclau T, Marcucio RS, Colnot C. Immunolocalization of BMPs, BMP antagonists, receptors, and effectors during fracture repair. Bone. 2010;46:841–51.

Article  CAS  PubMed  Google Scholar 

Kosa J