Tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA is constitutively expressed in bovine, human normal, and osteoarthritic articular chondrocytes.
Tissue inhibitors of metalloproteinases (TIMPs) inhibit the extracellular matrix (ECM) metalloproteinases (MMPs). To determine the source of TIMPs in synovial fluids of patients with osteoarthritis (OA), the ability of chondrocytes to express TIMP-2 and its regulation by agents found in inflammed joints was investigated. The constitutive TIMP-2 mRNA expression was demonstrated in chondrocytes from normal bovine, human OA and normal cartilage. The cross-hybridization of human and bovine TIMP-2 suggested its evolutionary conservation. Serum, IL-1, IL-6 and TGC-beta were unable to augment considerably the basal expression of TIMP-2 mRNA. TIMP-1 RNA expression in chondrocytes from human OA cartilage was elevated compared to non-OA chondrocytes, while TIMP-2 mRNA levels were similar in both. IL-1 beta, IL-6 and TGF-beta did not affect TIMP-2 expression but TGF-beta induced TIMP-1 mRNA in human OA chondrocytes. TIMP-2 and TIMP-1 are therefore differentially regulated in chondrocytes and the basal TIMP-2 levels may be needed for the cartilage ECM integrity.
Zafarullah
M
M
Unité Rhumatismale, Centre de Recherche Louis-Charles Simard Hôpital Notre-Dame, Département de Médecine, Université de Montréal, Quebec, Canada.
Su
S
S
Martel-Pelletier
J
J
DiBattista
J A
JA
Costello
B G
BG
Stetler-Stevenson
W G
WG
Pelletier
J P
JP
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D007378:Interleukins / Q000502:physiology; D061965:Matrix Metalloproteinase Inhibitors; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D011480:Protease Inhibitors / Q000378:metabolism*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D012016:Reference Values; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta / Q000502:physiology
D016207:Cytokines; D006023:Glycoproteins; D006133:Growth Substances; D007378:Interleukins; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2