BMP signaling stimulates chondrocyte maturation and the expression of Indian hedgehog

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
C D GrimsrudR J O'Keefe

Abstract

Mutant BMP receptors were transfected into cultured embryonic upper sternal chrondrocytes using retroviral vectors to determine if BMP signaling is required for chondrocyte maturation and the expression of a key regulatory molecule, Indian hedgehog (Ihh). Chondrocytes infected with replication competent avian retroviruses (RCAS) viruses carrying constitutive active (CA) BMPR-IA and BMPR-IB had enhanced expression of type X collagen and Ihh mRNA. Addition of PTHrP, a known inhibitor of chondrocyte maturation, abolished the expression of type X collagen, BMP-6, and Ihh mRNAs in control cells. In contrast, PTHrP treated cultures infected with of CA BMPR-IA or CA BMPR-IB had low levels of BMP-6 and type X collagen, but high levels of Ihh expression. Although dominant negative (DN) BMPR-IA had no effect, DN BMPR-IB inhibited the expression of type X collagen and BMP-6, and decreased alkaline phosphatase activity, even in the presence of exogenously added BMP-2 and BMP-6. DN BMPR-IB also completely blocked Ihh expression. Overall, the effect of DN BMPR-IB mimicked the effects of PTHrP. To determine if there is an autocrine role for the BMPs in chondrocyte maturation, the cultures were treated with noggin and follistatin, molecules th...Continue Reading

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