Melatonin (MLT) can increase the expression of cartilage-derived growth factor and stimulate the synthesis of cartilage matrix. To investigate the prevention and treatment effects of MLT on damaged cartilage through observing the expressions of bone morphogenetic protein 2 (BMP-2) and interleukin 1beta (IL-1beta) in articular cartilage of the rats with osteoarthritis (OA).
Forty SPF 4-week-old male SD rats (weighing 120-150 g) were randomly divided into 4 groups (n=10): normal control group (group A), OA group (group B), OA/pinealectomy group (group C), and OA/pinealectomy/MLT group (group D). The rats of group A served as a control without treatment. The rats of groups B, C, and D underwent left knee joint injection of 0.2 mL 4% papain solution 1 time every other day for 2 weeks for establishing OA model. Two weeks after papain injection, the rats of groups C and D were exposed to continuous light for 24 hours (intensity of illumination: 500 lx) for creating pinealectomy models. And at the next day after pinealectomy model establishing, the rats of group D were treated with intra-articular injections of 0.2 mL 20 mg/mL MLT solution 4 times a week for 4 weeks. At 1 week after last MLT injection, the venous blood samples were taken in groups A, B, and C to test the level of serum MLT by ELISA, respectively, and then the specimens of left cartilage of femoral condyle were harvested for macroscopic, histological, and immunohistochemical examinations in 4 groups.
The OA and pinealectomy models of rats were successfully established, and all rats survived. There were significant differences in the serum MLT level among groups A, B, and C, and among different time points at the same group (P < 0.05). In group A, articular cartilage surface was smooth and elastic, and chondrocytes arranged regularly. In groups B and C, articular cartilage surface was rough, cartilage defects and subchondral bone exposure were observed in some areas, and chondrocytes arranged irregularly. In group D, cartilage surface was more smooth than that in groups B and C, and the degrees of cartilage defect and subchondral bone exposure decreased with regular arrangement of chondrocytes. There were significant differences in Mankin scores and integral absorbance values among 4 groups (P < 0.05).
Exposure to continuous light can accelerate degeneration process of articular cartilage of OA rats. Injections of 0.2 mL MLT solution (20 mg/mL) by intra-articular for 4 weeks can inhibit the progress of cartilage defects. Upregulation of anabolic factor of BMP-2 as well as down-regulation of catabolic factors of IL-1beta is associated with cartilage repair in the pathological features of OA.