ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2010
rBMP represses Wnt signaling and influences skeletal progenitor cell fate specification during bone repair.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 57 citations in OpenAlex.
- Article
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- Genetic determinants of periosteum-mediated craniofacial bone regeneration: a systematic review.Archives of craniofacial surgery · 2023Article
- Periosteal Skeletal Stem and Progenitor Cells in Bone Regeneration.Current osteoporosis reports · 2022Review
- Myeloid-derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation.EMBO reports · 2022Article
- Osteoblast-derived EGFL6 couples angiogenesis to osteogenesis during bone repair.Theranostics · 2021Article
- MicroRNA-92a-1-5p influences osteogenic differentiation of MC3T3-E1 cells by regulating β-catenin.Journal of bone and mineral metabolism · 2019Article
- Bone morphogenetic proteins in fracture repair.International orthopaedics · 2018Review
- Article
- Digit Tip Regeneration: Merging Regeneration Biology with Regenerative Medicine.Stem cells translational medicine · 2018Article
- The periosteal requirement and temporal dynamics of BMP2-induced middle phalanx regeneration in the adult mouse.Regeneration (Oxford, England) · 2017Article
- From restoration to regeneration: periodontal aging and opportunities for therapeutic intervention.Periodontology 2000 · 2016Review
- [The expressions of the Notch and Wnt signaling pathways and their significance in the repair process of alveolar bone defects in rabbits with bone marrow stem cells compounded with platelet-rich fibrin].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2016Article
- Osteoblast-derived VEGF regulates osteoblast differentiation and bone formation during bone repair.The Journal of clinical investigation · 2016Article
- Novel Wnt Regulator NEL-Like Molecule-1 Antagonizes Adipogenesis and Augments Osteogenesis Induced by Bone Morphogenetic Protein 2.The American journal of pathology · 2016Article
- MiR-26a functions oppositely in osteogenic differentiation of BMSCs and ADSCs depending on distinct activation and roles of Wnt and BMP signaling pathway.Cell death & disease · 2015Article
- Biological aspects of segmental bone defects management.International orthopaedics · 2015Review
- The convergence of fracture repair and stem cells: interplay of genes, aging, environmental factors and disease.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2014Review
- The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing.International orthopaedics · 2014Review
- Sequential and opposing activities of Wnt and BMP coordinate zebrafish bone regeneration.Cell reports · 2014Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
Bone morphogenetic proteins (BMPs) participate in multiple stages of the fetal skeletogenic program from promoting cell condensation to regulating chondrogenesis and bone formation through endochondral ossification. Here, we show that these pleiotropic functions are recapitulated when recombinant BMPs are used to augment skeletal tissue repair. In addition to their well-documented ability to stimulate chondrogenesis in a skeletal injury, we show that recombinant BMPs (rBMPs) simultaneously suppress the differentiation of skeletal progenitor cells in the endosteum and bone marrow cavity to an osteoblast lineage. Both the prochondrogenic and antiosteogenic effects are achieved because rBMP inhibits endogenous beta-catenin-dependent Wnt signaling. In the injured periosteum, this repression of Wnt activity results in sox9 upregulation; consequently, cells in the injured periosteum adopt a chondrogenic fate. In the injured endosteum, rBMP also inhibits Wnt signaling, which results in the runx2 and collagen type I downregulation; consequently, cells in this region fail to differentiate into osteoblasts. In muscle surrounding the skeletal injury site, rBMP treatment induces Smad phosphorylation followed by exuberant cell proliferation, an increase in alkaline phosphatase activity, and chondrogenic differentiation. Thus different populations of adult skeletal progenitor cells interpret the same rBMP stimulus in unique ways, and these responses mirror the pleiotropic effects of BMPs during fetal skeletogenesis. These mechanistic insights may be particularly useful for optimizing the reparative potential of rBMPs while simultaneously minimizing their adverse outcomes.
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