Original Article
You have full text access to this OnlineOpen article
rBMP represses Wnt signaling and influences skeletal progenitor cell fate specification during bone repair
Article first published online: 15 JAN 2010
DOI: 10.1002/jbmr.29
Copyright © 2010 American Society for Bone and Mineral Research
Additional Information
How to Cite
Minear, S., Leucht, P., Miller, S. and Helms, J. A. (2010), rBMP represses Wnt signaling and influences skeletal progenitor cell fate specification during bone repair. J Bone Miner Res, 25: 1196–1207. doi: 10.1002/jbmr.29
Publication History
- Issue published online: 27 MAY 2010
- Article first published online: 15 JAN 2010
- Accepted manuscript online: 15 JAN 2010 12:00AM EST
- Manuscript Accepted: 6 JAN 2010
- Manuscript Revised: 18 SEP 2009
- Manuscript Received: 27 APR 2009
References
- 1, , , , . 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. 2002; 16: 2813–2828.
- 2, , , , . Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997; 89: 747–754.
- 3, , , et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997; 89: 755–764.
- 4, , , et al. Dicer-dependent pathways regulate chondrocyte proliferation and differentiation. Proc Natl Acad Sci U S A. 2008; 105: 1949–1954.
- 5, , , , , . Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science. 1996; 273: 613–622.
- 6, , . Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes and Development. 1999; 13: 2072–2086.
- 7, , , et al. PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth (see comments). Science. 1996; 273: 663–666.
- 8, , , et al. An integrative genetics approach to identify candidate genes regulating BMD: combining linkage, gene expression, and association. J Bone Miner Res. 2009; 24: 105–116.Direct Link:
- 9, , , et al. Comprehensive microarray analysis of bone morphogenetic protein 2–induced osteoblast differentiation resulting in the identification of novel markers for bone development. J Bone Miner Res. 2002; 17: 2106–2118.Direct Link:
- 10, , , , . Microarray analyses of gene expression during chondrocyte differentiation identifies novel regulators of hypertrophy. Mol Biol Cell. 2005; 16: 5316–5333.
- 11, . BMP signaling in the cartilage growth plate. Curr Top Dev Biol. 2006; 76: 1–48.
- 12. Bone: Formation by autoinduction. Science. 1965; 150: 893.
- 13
- 14, . Divide, accumulate, differentiate: cell condensation in skeletal development revisited. International Journal of Developmental Biology. 1995; 39: 881–893.
- 15, , , . BMP canonical Smad signaling through Smad1 and Smad5 is required for endochondral bone formation. Development. 2009; 136: 1093–1104.
- 16, , , et al. Twisted gastrulation modulates bone morphogenetic protein-induced collagen II and X expression in chondrocytes in vitro and in vivo. J Biol Chem. 2006; 281: 31790–31800.
- 17, , , et al. BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway. Development. 2008; 135: 3801–3811.
- 18, , , et al. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am. 2002; 84-: 2123–2134.
- 19, , , , . Recombinant human bone morphogenetic protein-7 induces healing in a canine long-bone segemental defect model. CORR. 1994; 301: 302–312.
- 20, , , . The effect of osteogenic protein-1 on the healing of segmental bone defects treated with autograft or allograft bone. J Bone Joint Surg Am. 2001; 83-A: 803–816.
- 21, , . Bone morphogenetic proteins in clinical applications. Aust NZ J Surg. 2007; 77: 626–631.Direct Link:
- 22, . Medtronic Product Linked to Surgery Problems Wall Street Journal. Wall Street Journal, New York City. 2008.
- 23, , , , , . Application of recombinant BMP-7 on persistent upper and lower limb non-unions. Injury. 2005; 36 (Suppl 4): S51–59.
- 24, , , et al. Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am. 2001; 83-A (Suppl 1): S151–158.
- 25, , , , , . A prospective randomized study of posterolateral lumbar fusion using osteogenic protein-1 (OP-1) versus local autograft with ceramic bone substitute: emphasis of surgical exploration and histologic assessment. Spine. 2006; 31: 1067–1074.
- 26, , , et al. Effect of recombinant human bone morphogenetic protein-2 on fracture healing in a goat tibial fracture model. Journal of Bone and Mineral Research. 1998; 13: 1483–1490.Direct Link:
- 27, . BMP-2 can inhibit bone healing. Bone-chamber study in rabbits. Acta Orthop Scand. 1996; 67: 589–592.
- 28, , , et al. Healing segmental femoral defects in sheep using recombinant human bone morphogenetic protein. Clin Orthop. 1993; 293: 317–326.
- 29
- 30, , , , . Self-renewal and expansion of single transplanted muscle stem cells. Nature. 2008; 456: 502–506.
- 31, . Skeletal stem/osteoprogenitor cells: current concepts, alternate hypotheses, and relationship to the bone remodeling compartment. J Cell Biochem. 2008; 103: 393–400.Direct Link:
- 32, , , et al. Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Mol Cell Biol. 2002; 22: 1184–1193.
- 33, , , , , . Wnt/β-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol. 2002; 22: 1172–1183.
- 34, , , et al. Bone regeneration is regulated by Wnt signaling. J Bone Miner Res. 2007; 22: 1913–1923.Direct Link:
- 35, , . Beta-catenin-dependent Wnt signaling in mandibular bone regeneration. J Bone Joint Surg Am. 2008; 90 (Suppl 1): 3–8.
- 36, , , , . Embryonic origin and Hox status determine progenitor cell fate during adult bone regeneration. Development. 2008; 135: 2845–2854.
- 37, . Effects of recombinant human fibroblast growth factor-2 on osteogenic cell populations during orthopic osteogenesis in vivo. Bone. 2000; 26: 161–168.
- 38, , , et al. Recombinant human bone morphogenetic protein-2 accelerates healing in a rabbit ulnar osteotomy model. J Bone Joint Surg Am. 2001; 83-A: 1219–1230.
- 39, , , , . Translating insights from development into regenerative medicine: The function of Wnts in bone biology. Semin Cell Dev Biol. 2008; 19: 434–443.
- 40, , , et al. Stimulatory effect of bone morphogenetic protein-2 on osteoclast-like cell formation and bone-resorbing activity. J Bone Miner Res. 1995; 10: 1681–1690.Direct Link:
- 41, , , et al. The role of Axin2 in calvarial morphogenesis and craniosynostosis. Development. 2005; 132: 1995–2005.
- 42, , . Craniosynostosis caused by Axin2 deficiency is mediated through distinct functions of β-catenin in proliferation and differentiation. Dev Biol. 2007; 301: 298–308.
- 43, , , et al. Expression of collagen, osteocalcin, and bone alkaline phosphatase in a mineralizing rat osteoblastic cell culture. Calcif Tissue Int. 1992; 50: 175–183.
- 44, , , . RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med. 2006; 12: 17–25.
- 45, , , . Wnt and FGF signals interact to coordinate growth with cell fate specification during limb development. Development. 2008; 135: 3247–3257.
- 46, , , , , . Transcriptional mechanisms of chondrocyte differentiation. Matrix Biol. 2000; 19: 389–394.
- 47, , , et al. SOX9 directly regulates the type-II collagen gene. Nature Genetics. 1997; 16: 174–178.
- 48, , , . Distribution of type I and type II collagen gene expression during the development of human long bones. Bone. 1990; 11: 275–279.
- 49, , , . A model for intramembranous ossification during fracture healing. J Orthop Res. 2002; 20: 1091–1098.Direct Link:
- 50, , , , . Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism. Ann Rheum Dis. 2008; 67 (Suppl 3): iii75–82.
- 51, , , et al. Mechanical tension-stress induces expression of bone morphogenetic protein (BMP)-2 and BMP-4, but not BMP-6, BMP-7, and GDF-5 mRNA, during distraction osteogenesis. J Bone Miner Res. 1999; 14: 1084–1095.Direct Link:
- 52. Skeletal Cell Fate Decisions Within Periosteum and Bone Marrow During Bone Regeneration. J Bone Miner Res. 2008; 24: 274–282.Direct Link:
- 53, , , et al. Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal. Cell. 2007; 131: 980–993.
- 54, , . Wnt signaling in Xenopus embryos inhibits bmp4 expression and activates neural development. Genes Dev. 1999; 13: 3149–3159.
- 55, . Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development. 2006; 133: 3231–3244.
- 56, , , et al. Beta-catenin signaling plays a disparate role in different phases of fracture repair: implications for therapy to improve bone healing. PLoS Med. 2007; 4: e249.
- 57, . Where Wnts went: the exploding field of Lrp5 and Lrp6 signaling in bone. J Bone Miner Res. 2009; 24: 171–178.Direct Link:
- 58, , , . Characterization of cells with osteogenic potential from human marrow. Bone. 1992; 13: 81–88.
- 59, . Autologous iliac crest bone graft: Should it still be the gold standard for treating nonunions? Injury. 2007; 38 (Suppl 1): S75–80.
- 60, , , . Regulation of BMP-induced transcription in cultured human bone marrow stromal cells. J Bone Joint Surg Am. 2003; 85-A (Suppl 3): 19–28.
- 61, , , . BMP responsiveness in human mesenchymal stem cells. Connect Tissue Res. 2003; 44 (Suppl 1): 305–311.
- 62, , , . Different effects of BMP-2 on marrow stromal cells from human and rat bone. Cells Tissues Organs. 2004; 176: 109–119.
- 63, , , 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 Am. 2006; 88: 1431–1441.
- 64, , , et al. Canonical WNT signaling promotes osteogenesis by directly stimulating runx2 gene expression. J Biol Chem. 2005; 280: 33132–33140.
- 65, , , et al. Cbfa1 as a regulator of osteoblast differentiation and function. Bone. 1999; 25: 107–108.
- 66, . LRP5 mutations linked to high bone mass diseases cause reduced LRP5 binding and inhibition by SOST. J Biol Chem. 2006.
- 67, , , et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. Embo J. 2003; 22: 6267–6276.
- 68, , , , . Osteocyte-derived sclerostin inhibits bone formation: its role in bone morphogenetic protein and Wnt signaling. J Bone Joint Surg Am. 2008; 90 (Suppl 1): 31–35.
- 69, , , et al. Periosteal progenitor cell fate in segmental cortical bone graft transplantations: implications for functional tissue engineering. J Bone Miner Res. 2005; 20: 2124–2137.Direct Link:
- 70, , . Ectopic bone formation induced by biodegradable hydrogels incorporating bone morphogenetic protein. J Biomater Sci Polym Ed. 1998; 9: 439–458.
- 71, , , et al. A novel biodegradable delivery system for bone morphogenetic protein-2. Plast Reconstr Surg. 2008; 121: 1920–1928.
- 72, , , , . Impact of stromal cell composition on BMP-induced chondrogenic differentiation of mouse bone marrow derived mesenchymal cells. Exp Cell Res. 2008; 314: 2400–2410.

1523-4681/asset/olbannerleft.gif?v=1&s=d7e4c0e37904a489128d3a4e58ba94214db307a9)
1523-4681/asset/olbannerright.gif?v=1&s=854ee0e4d351ead9faaca8bfab3e50b1c7c9d03d)
