BMP-2 and TGF-β1 differentially control expression of type II procollagen and α10 and α11 integrins in mouse chondrocytes

Bone morphogenetic protein (BMP)-2 and transforming growth factor (TGF)-beta 1 are multifunctional cytokines both proposed as stimulants for cartilage repair Thus it is crucial to closely examine and compare their effects on the expression of key markers of the chondrocyte phenotype, at the gene and protein level. In this study, the expression of alpha 10 and alpha 11 integrin subunits and the IIA/IIB spliced forms of type II procollagen have been monitored for the first time in parallel in the same in vitro model of mouse chondrocyte dedifferentiation/redifferentiation We demonstrated that TGF-111 stimulates the expression of the non-chondrogenic form of type II procollagen, IIA isoform, and of a marker of mesenchymal tissues, le the all integrin subunit. On the contrary, BMP-2 stimulates the cartilage-specific form of type II procollagen, IIB isoform, and a specific marker of chondrocytes, i e the alpha 10 integrin subunit. Collectively, our results demonstrate that BMP-2 has a better capability than TGF-111 to stimulate chondrocyte reclifferentiation and reveal that the relative expressions of type IIB to type IIA procollagens and alpha 10 to alpha 11 integrin subunits are good markers to define the differentiation state of chondiocytes In addition, adenoviral expression of Smac16, an inhibitor of BMP canonical Smad signaling, did not affect expression of total type II procollagen or the ratio of type IIA and type IIB isoforms in mouse chondrocytes exposed to BMP-2 This result strongly suggests that signaling pathways other than Smad proteins are involved in the effect of BMP-2 on type II procollagen expression (C) 2010 Elsevier GmbH All rights reserved