Bmpr1a and Bmpr1b Essential for Cartilage Formation
Mar 30, 2005 - 6:44:38 AM
Byeong Yoon et al. report that bone morphogenetic protein (BMP) signaling is essential for the generation of chondrocytes in vivo.
During development, chondrocytes proliferate and form the cartilage that acts as the template for bone formation. Previous studies have demonstrated that BMPs can promote differentiation of chondrocytes in vitro.
To clarify the in vivo role of BMP signaling during chondrocyte development, Yoon et al. generated mice lacking the BMP receptors Bmpr1a and Bmpr1b in chondrocytes. The researchers showed that mice deficient in either Bmpr1a or Bmpr1b were able to form cartilage elements and had few skeletal defects, but Bmpr1a/Bmpr1b double mutants developed severe generalized chondrodysplasia, including delayed bone formation and shortened long bones.
Cartilage condensations in double mutants were reduced in size because of decreased proliferation and increased apoptosis. The few cartilage condensations that developed were arrested in the prechondrocytic stage and never formed an organized growth plate. In addition, the mutant cartilage lacked Sox9, a transcription factor involved in early chondrocyte differentiation, as well as the downstream targets of Sox9, L-Sox5, and Sox6.
The authors conclude that Bmpr1a and Bmpr1b are functionally redundant during early chondrogenesis, and that BMP signaling is required for chondrocyte proliferation, survival, and differentiation in vivo.
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