The New Collagenase, Collagenase-3, Is Expressed and Synthesized by Human Chondrocytes but not by Synoviocytes A Role in Osteoarthritis

Abstract : Recently, a new human collagenase, collagenase-3 has been identified. Since collagen changes are of particular importance in cartilage degeneration, we investigated if collagenase-3 plays a role in osteoarthritis (OA). Reverse transcriptase–PCR analysis revealed that in ar-ticular tissues collagenase-3 was expressed by the chondro-cytes but not by the synoviocytes. Northern blot analysis of the chondrocyte mRNA revealed the presence of two major gene transcripts of 3.0 and 2.5 kb, and a third one of 2.2 kb was occasionally present. Compared to normal, OA showed a significantly higher (3.0 kb, P 0.05; 2.5 kb, P 0.03) level of collagenase-3 mRNA expression. Collagenase-3 had a higher catalytic velocity rate (about fivefold) than collage-nase-1 on type II collagen. With the use of two specific anti-bodies, we showed that human chondrocytes had the ability to produce collagenase-3 as a proenzyme and as a glycosy-lated doublet. The chondrocyte collagenase-3 protein is produced in a significantly higher (P 0.04) level in OA (9.5-fold) than in normal. The synthesis and expression of this new collagenase could also be modulated by two proinflam-matory cytokines, IL-1 and TNF-, in a time-and dose-dependent manner. This study provides novel and interesting data on collagenase-3 expression and synthesis in human cartilage cells and suggest its involvement in human OA cartilage patho-physiology.
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P. Reboul, Jean-Pierre Pelletier, Ginette Tardif, Jean-Marie Cloutier, Johanne Martel-Pelletier. The New Collagenase, Collagenase-3, Is Expressed and Synthesized by Human Chondrocytes but not by Synoviocytes A Role in Osteoarthritis. Journal of Clinical Investigation, American Society for Clinical Investigation, 1996, 97 (9), pp.2011-2019. ⟨10.1172/JCI118636⟩. ⟨hal-01705146⟩

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