Factors related to degradation of articular cartilage in osteoarthritis: a review.
OBJECTIVE
Osteoarthritis (OA) is a common joint deterioration initiated by multiple factors. To better understand related factors in the development of this disease, we focused on the mechanical stress loaded on articular cartilage.


METHODS
The anterior cruciate ligaments of rabbit knee joints were transected, and expression of protein kinase C (PKC) examined immunohistochemically. The PKC activator 12-o-tetradecanoyl-phorbol-13-acetate (TPA) was then administered intraarticularly. To determine the involvement of gas mediators, a cartilage defect was made on the medical femoral condyle of rabbit knee joints. Hydrostatic pressure was loaded on the cartilage taken from the surrounding defects, and levels of superoxide anion and nitric oxide (NO) were measured. Bovine chondrocytes were subjected to cyclic mechanical stretch using a Flexercell Strain Instrument. Proteoglycan synthesis and PKC activity were measured. Expression of matrix metalloproteinase (MMP)-3 and tissue inhibitor of metalloproteinase (TIMP)-1 in articular cartilages obtained from OA patients were examined using Northern blots.


RESULTS
Chondrocytes from experimentally induced OA were stained positively with anti-alpha-PKC antibody. Intraarticular administration of TPA prevented the development of OA changes. Cyclic tensile stretch loaded on chondrocytes decreased proteoglycan synthesis and PKC activity. Thus, PKC is involved in the stress-mediated degradation of articular cartilage. Cartilage defects led to degradation of surrounding cartilage and to enhanced superoxide anion and NO synthesis. We also noted increased and decreased expressions of MMP-3 and TIMP-1 mRNA in human OA cartilage, respectively.


CONCLUSIONS
PKC, gas mediators (superoxide anion, NO), and proteinases are all involved in OA.
Tanaka
S
S
Department of Orthopaedic Surgery, Kinki University School of Medicine, Osaka, Japan.
Hamanishi
C
C
Kikuchi
H
H
Fukuda
K
K
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D004195:Disease Models, Animal; D006801:Humans; D007632:Keratan Sulfate / Q000097:blood; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D013314:Stress, Mechanical; D013481:Superoxides / Q000378:metabolism; D013718:Tensile Strength; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D019715:Tissue Inhibitor of Metalloproteinase-1; D013481:Superoxides; D009569:Nitric Oxide; D007632:Keratan Sulfate; D011493:Protein Kinase C; D019278:Matrix Metalloproteinase 3; D013755:Tetradecanoylphorbol Acetate