Stimulation of TIMP-1 production by oncostatin M in human articular cartilage.
OBJECTIVE
To investigate the effects of the interleukin-6 (IL-6) family cytokines, such as IL-6, IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OSM), on the production of tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) in human articular cartilage.


METHODS
Effects of IL-6 family cytokines and growth factors on TIMP-1 production were studied in human articular chondrocytes, grown as monolayer and cartilage explant culture. TIMP-1 protein levels in the cultured medium were measured by sandwich enzyme immunoassay. TIMP-1 messenger RNA levels in the cultured chondrocytes were analyzed by Northern blotting. Western blot analysis was performed to evaluate the release of matrix metalloproteinases (MMPs) in the cultured medium. Cell proliferation of chondrocytes was determined by 3H-thymidine uptake.


RESULTS
IL-6 family cytokines induced TIMP-1 expression in monolayer and explant culture, and the production of TIMP-1 was most stimulated by OSM. In contrast, OSM did not modulate the release of MMPs and cell proliferation.


CONCLUSIONS
These results suggest that OSM may be characterized as one of the chondroprotective mediators in cartilage destruction.
Nemoto
O
O
National Defense Medical College, Saitama, Japan.
Yamada
H
H
Mukaida
M
M
Shimmei
M
M
D000328:Adult; D000595:Amino Acid Sequence; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D006023:Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008666:Metalloendopeptidases / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000378:metabolism*; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases
D016207:Cytokines; D006023:Glycoproteins; D006133:Growth Substances; C508351:OSM protein, human; D010455:Peptides; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D053683:Oncostatin M; D008666:Metalloendopeptidases