The levels of collagenase, tissue inhibitor of metalloproteinases-1 (TIMP-1), collagenase approximately TIMP-1 complexes and glycosaminoglycan (GAG) in sequential samples of synovial fluid aspirated from patients with osteoarthritis.
OBJECTIVE
Collagen turnover in connective tissues is thought to be controlled by the balance between the levels of interstitial collagenase and tissue inhibitor of metalloproteinases (TIMP-1). The aim of this study was to measure the level of total collagenase (MMP-1), TIMP-1, collagenase approximately TIMP-1 complex and glycosaminoglycan (GAG) in sequential samples of osteoarthritic knee synovial fluid from well documented patients to determine if these parameters changed with time and correlated with clinical indices.


METHODS
Twenty-one patients were recruited and randomly allocated to receive tiaprofenic acid, indomethacin or naproxen. Total collagenase, TIMP-1, collagenase approximately TIMP-1 complex and GAG were measured in 80 osteoarthritic synovial fluids taken over a period of six months.


RESULTS
The majority of fluids contained a molar excess of TIMP-1 over collagenase, although in seven fluids collagenase was present in excess; six of these samples were from a single patient. GAG levels were relatively unchanged over the six months studied.


CONCLUSIONS
The levels of collagenase and TIMP-1 varied between patients and over time in individual patients. No collagenase approximately TIMP-1 complex was found in any fluid. There was no significant difference in the median levels of collagenase, TIMP-1 or GAG in the different treatment groups. High levels of collagenase were found in one patient with a crystal related disease. These immunoassays give valuable information on the levels of collagenase and TIMP-1 in individual patients with time and may help to determine the mechanisms controlling the turnover of cartilage collagen in different arthritides.
Cawston
T E
TE
Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, UK.
Curry
V
V
Ramsey
S
S
Clark
I M
IM
Kyle
V A
VA
Adebajo
A
A
Silverman
B
B
Daymond
T
T
Hazleman
B L
BL
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D017364:Collagenases / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use; D007719:Knee Joint; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D009288:Naproxen / Q000627:therapeutic use; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism*; D011422:Propionates / Q000627:therapeutic use; D013396:Suction; D013582:Synovial Fluid / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006023:Glycoproteins; D006025:Glycosaminoglycans; D061965:Matrix Metalloproteinase Inhibitors; D011422:Propionates; D019714:Tissue Inhibitor of Metalloproteinases; C021270:tiaprofenic acid; D009288:Naproxen; D017364:Collagenases; D007213:Indomethacin