Modulation of collagen synthesis in normal and osteoarthritic cartilage

摘要

In osteoarthritic cartilage, chondrocytes are able to present heterogeneous cellular reactions with expression and synthesis of the (pro)collagen types characteristic of prechondrocytes (type ⅡA), hypertrophic chondrocytes (type X), as well as differentiated (types ⅡB, Ⅸ, Ⅺ, Ⅵ) and dedifferentiated (types Ⅰ, Ⅲ) chondrocytes. The expression of type ⅡA procollagen in human osteoarthritic cartilage support the assumption that OA chondrocytes reverse their phenotype towards a chondroprogen-itor phenotype. Recently, we have shown that dedifferentiation of mouse chondrocytes induced by subculture was associated with the alternative splicing of type Ⅱ procollagen pre-mRNA with a switch from the ⅡB to the ⅡA form. In this context, we demonstrated that BMP-2 favours expression of type ⅡB whereas TGF-β1 potentiates expression of type ⅡA induced by subculture. These data reveal the specific capability of BMP-2 to reverse the program of chondrocyte dedifferentiation. This interesting feature needs to be tested with human chondrocytes since cell amplification is required for the currently used autol-ogous chondrocyte transplantation.