Matrix metalloproteinase-3 inhibitor I accelerates the early-stage repair of full-thickness articular cartilage defects in the knee of rats / 中国组织工程研究

ABSTRACT

BACKGROUND:The biomechanical properties of naturaly regenerated damaged articular cartilage that belongs to the fibrovascular tissue are far worse than those of the normal cartilage so that they cannot meet the requirements for joint function, leading to traumatic arthritis and loss of joint function. OBJECTIVE:To evaluate the effects of matrix metaloproteinase-3 (MMP-3) inhibitor I with different concentrations on the early-stage repair of ful-thickness articular cartilage defects in the knee of rats. METHODS: Twenty-four Sprague Dawley rats were randomized into control, defect (DEF), and defect combined with low-(D+L) and high-dose inhibitor (D+H) groups (n=6 for each group), respectively. Full-thickness articular cartilage defects followed by intraarticular injection of low- and high-dose MMP-3 inhibitor I for 4 weeks was administered in the later two groups. Serum MMP-3 was detected using ELISA method before and after experiment, respectively. Femoral trochleas were collected to observe characteristics of repaired tissue by gross appearance scoring and O’Driscoll histological scoring with Safranine O-Fast Green staining, and to measure type II colagen by immunohistochemistry after experiment. RESULTS AND CONCLUSION:Rats in the D+H group had obvious repair similarly to hyaline articular cartilage, while creamy white cartilage tissue and fibrous tissue repair were observed in D+L group and in DEF group. D+H group obtained the best repair results according to gross appearance scoring and O’Driscol histological scoring and the highest content of type II colagen (P< 0.05). MMP-3 concentration and the difference value before and after experiment were gradualy decreased in DEF, D+L, D+H, and control groups in sequence(P< 0.05). These findings demonstrate that MMP-3 inhibitor I accelerates the early-stage repair of ful-thickness articular cartilage defects in the knee of rats.