Prostromelysin and procollagenase genes are differentially up-regulated in chondrocytes from the knees of rabbits with experimental osteoarthritis.
OBJECTIVE
To determine the relative expressions of matrix metalloprotease (MMP) genes pro-MMP1 and pro-MMP3 in the cartilage of rabbits with experimentally induced osteoarthritis (OA), and to assess the role of the chondrocyte in this process.


METHODS
OA was induced in rabbits after partial medial meniscectomy. Rabbits were killed at 4 weeks or 8 weeks, and total cellular RNA was prepared from cartilage and probed by Northern blotting with pro-MMP 32P-labeled complementary DNA. Monolayer chondrocytes were used to assess MMP-inducing activity of chondrocyte factor(s).


RESULTS
Pro-MMP messenger RNAs (mRNAs) were up-regulated in experimental OA cartilage; pro-MMP3 mRNA expression exceeded that of pro-MMP1. Conditioned medium from OA-derived chondrocytes up-regulated pro-MMP mRNAs in normal chondrocytes.


CONCLUSIONS
Up-regulation of MMP genes in this OA model may contribute to cartilage degradation. Chondrocytes up-regulate MMP genes via an autocrine pathway.
Mehraban
F
F
Case Western Reserve University School of Medicine, Cleveland, Ohio.
Kuo
S Y
SY
Riera
H
H
Chang
C
C
Moskowitz
R W
RW
D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D002358:Cartilage, Articular / Q000166:cytology* / Q000502:physiology; D017364:Collagenases / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D007719:Knee Joint; D019278:Matrix Metalloproteinase 3; D008592:Menisci, Tibial / Q000601:surgery; D008666:Metalloendopeptidases / Q000235:genetics*; D010003:Osteoarthritis / Q000209:etiology / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D015854:Up-Regulation
D011498:Protein Precursors; D012333:RNA, Messenger; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3