BMPs regulate multiple aspects of growth-plate chondrogenesis through opposing actions on FGF pathways

Citations Over TimeTop 10% of 2006 papers

Abstract

Bone morphogenetic protein (BMP) signaling pathways are essential regulators of chondrogenesis. However, the roles of these pathways in vivo are not well understood. Limb-culture studies have provided a number of essential insights, including the demonstration that BMP pathways are required for chondrocyte proliferation and differentiation. However, limb-culture studies have yielded contradictory results; some studies indicate that BMPs exert stimulatory effects on differentiation, whereas others support inhibitory effects. Therefore, we characterized the skeletal phenotypes of mice lacking Bmpr1a in chondrocytes (Bmpr1a(CKO)) and Bmpr1a(CKO);Bmpr1b+/- (Bmpr1a(CKO);1b+/-) in order to test the roles of BMP pathways in the growth plate in vivo. These mice reveal requirements for BMP signaling in multiple aspects of chondrogenesis. They also demonstrate that the balance between signaling outputs from BMP and fibroblast growth factor (FGF) pathways plays a crucial role in the growth plate. These studies indicate that BMP signaling is required to promote Ihh expression, and to inhibit activation of STAT and ERK1/2 MAPK, key effectors of FGF signaling. BMP pathways inhibit FGF signaling, at least in part, by inhibiting the expression of FGFR1. These results provide a genetic in vivo demonstration that the progression of chondrocytes through the growth plate is controlled by antagonistic BMP and FGF signaling pathways.

Related Papers

• → Temporal and spatial regulation of bone morphogenetic protein signaling in late lung development(2007)37 cited
• → Deletion of the Sequence Encoding the Tail Domain of the Bone Morphogenetic Protein type 2 Receptor Reveals a Bone Morphogenetic Protein 7-Specific Gain of Function(2013)10 cited
• → Insight into Molecular Mechanism for Activin A-Induced Bone Morphogenetic Protein Signaling(2020)9 cited
• → Does BMPR2 Mutation Disrupt Pulmonary Vasculogenesis?(2005)3 cited
• → Bone morphogenetic protein (BMP) and SMAD signalling is important in the development of the human pulmonary vasculature(2004)