The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint.
OBJECTIVE
To study the interaction of interleukin-1alpha (IL-1alpha) and oncostatin M (OSM) in promoting cartilage collagen destruction.


METHODS
Bovine, porcine, and human cartilage and human chondrocytes were studied in culture. The levels of collagenase (matrix metalloproteinase 1 [MMP-1]) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by bioassay and enzyme-linked immunosorbent assay (ELISA). The levels of OSM in rheumatoid synovial fluid were measured by ELISA.


RESULTS
When combined with OSM, IL-1alpha, IL-1beta, and tumor necrosis factor alpha released proteoglycan and collagen from cartilage. OSM was the only member of the IL-6 family to have this effect. Human tendon also responded to IL-1alpha and OSM. OSM increased the production of MMP-1 and TIMP-1 but when combined with IL-1alpha, synergistically promoted MMP-1 production in human chondrocytes and synovial fibroblasts. High levels of OSM were found in human rheumatoid synovial fluids, and confocal microscopy showed that OSM was produced by macrophages in rheumatoid synovial tissue.


CONCLUSIONS
These results highlight an important new mechanism by which there is irreversible loss of collagen from cartilage.
University of Newcastle, Newcastle Upon Tyne, UK.
T E
TE
Cawston
V A
VA
Curry
C A
CA
Summers
I M
IM
Clark
G P
GP
Riley
P F
PF
Life
J R
JR
Spaull
M B
MB
Goldring
P J
PJ
Koshy
A D
AD
Rowan
W D
WD
Shingleton
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002417:Cattle; D019902:Chondrocytes / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D003238:Connective Tissue / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007719:Knee Joint / Q000737:chemistry; D018613:Microscopy, Confocal; D053683:Oncostatin M; D010003:Osteoarthritis / Q000378:metabolism; D010455:Peptides / Q000502:physiology*; D010641:Phenotype; D013552:Swine; D013582:Synovial Fluid / Q000737:chemistry; D013583:Synovial Membrane / Q000737:chemistry / Q000378:metabolism; D013710:Tendons / Q000187:drug effects
D016207:Cytokines; D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; C508351:OSM protein, human; D010455:Peptides; D053683:Oncostatin M; D003094:Collagen; D017364:Collagenases