Protein kinase C activator inhibits progression of osteoarthritis induced in rabbit knee joints

To study the role of protein kinase C (PKC) in cartilage tissue in osteoarthritis, experimental osteoarthritis was induced in the knee joints of rabbits by resection of the anterior cruciate ligament (ACL). At 4 weeks after the operation, osteoarthritic changes varying from surface irregularities and cleft formation to loss of the tangential layer were observed, and cloning or hypocellularity of the chondrocytes was observed mainly in the transitional and radial layers. The PKC activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or non-PKC-activating phorbol ester 4 alpha-phorbol-12,13-didecanate (PDD) was administered intraarticularly once a week from the day of the operation for 3 weeks. Histologic evaluation with a rating scale was carried out. In the TPA-administered group, cartilage structures were preserved almost completely, and score of the cartilage lesion was significantly less than that in animals administered PDD or in nonadministered controls. A chondroprotective role of PKC under mechanical stress was suggested.