The new collagenase, collagenase-3, is expressed and synthesized by human chondrocytes but not by synoviocytes. A role in osteoarthritis.
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 articular tissues collagenase-3 was expressed by the chondrocytes 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 < or = 0.05; 2.5 kb, P < or = 0.03) level of collagenase-3 mRNA expression. Collagenase-3 had a higher catalytic velocity tate (about fivefold) than collagenase-1 on type II collagen. With the use of two specific antibodies, we showed that human chondrocytes had the ability to produce collagenase-3 as a proenzyme and as a glycosylated doublet. The chondrocyte collagenase-3 protein is produced in a significantly higher (P < or = 0.04) level in OA (approximately 9.5-fold) than in normal. The synthesis and expression of this new collagenase could also be modulated by two proinflammatory cytokines, IL-1 beta and TNF-alpha, 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.
Reboul
P
P
University of Montreal, Rheumatology/Osteoarthritis Research Unit, L-C. Simard Research Center, Notre-Dame Hospital, Montreal, Quebec, Canada.
Pelletier
J P
JP
Tardif
G
G
Cloutier
J M
JM
Martel-Pelletier
J
J
D000368:Aged; D001483:Base Sequence; D002356:Cartilage / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis* / Q000302:isolation & purification; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D007719:Knee Joint / Q000201:enzymology* / Q000473:pathology; D053509:Matrix Metalloproteinase 13; D008875:Middle Aged; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000201:enzymology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D013583:Synovial Membrane / Q000201:enzymology* / Q000473:pathology
D016207:Cytokines; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13