Modulation of collagen synthesis in normal and osteoarthritic cartilage.
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 chondroprogenitor 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-beta1 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 autologous chondrocyte transplantation.
Institut de Biologie et Chimie des Protéines, Lyon, France.
Jérôme
J
Gouttenoire
Ulrich
U
Valcourt
Marie-Claire
MC
Ronzière
Elisabeth
E
Aubert-Foucher
Frédéric
F
Mallein-Gerin
Daniel
D
Herbage
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002358:Cartilage, Articular; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D003094:Collagen / Q000096:biosynthesis*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D010003:Osteoarthritis / Q000378:metabolism*; D011347:Procollagen / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011347:Procollagen; D016212:Transforming Growth Factor beta; D003094:Collagen