Osteoarthritic lesions: involvement of three different collagenases.
OBJECTIVE
To assess the presence of fibroblast collagenase (MMP-1), neutrophil collagenase (MMP-8), and collagenase 3 (MMP-13) in osteoarthritic (OA) cartilage, with particular emphasis on areas of macroscopic cartilage erosion.


METHODS
Messenger RNA (mRNA) levels were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization, and Northern blot analysis.


RESULTS
MMP-1 and MMP-13 were expressed at higher levels by OA chondrocytes than by normal chondrocytes. In addition, mRNA for MMP-8 was present in OA cartilage but not normal cartilage by PCR and Northern blot analyses. Chondrocytes from areas surrounding the OA lesion expressed greater quantities of MMP-1 and MMP-13 compared with normal chondrocytes, suggesting local modulation by mechanical and inflammatory factors. Tumor necrosis factor alpha stimulated the expression of all 3 collagenases. Retinoic acid, an agent which induces autodigestion of cartilage in vitro, stimulated only the expression of MMP-13.


CONCLUSIONS
These findings suggest a key role of MMP-13 and MMP-8, as well as MMP-1 in osteoarthritis.
Shlopov
B V
BV
University of Tennessee, Memphis, USA.
Lie
W R
WR
Mainardi
C L
CL
Cole
A A
AA
Chubinskaya
S
S
Hasty
K A
KA
D000368:Aged; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002358:Cartilage, Articular / Q000201:enzymology*; D017364:Collagenases / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D020781:Matrix Metalloproteinase 1; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020784:Matrix Metalloproteinase 8; D008875:Middle Aged; D010003:Osteoarthritis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017931:DNA Primers; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1