**3.2 Insulin-like growth factor-I (IGF-I)**

IGF-1 is a multifunctional growth factor. The studies have found that IGF-1 play an important role in maintaining articular cartilage integrity. IGF-I deficiency has led to the development of articular lesions [53]. IGF-1 can not only enhance the synthesis of proteoglycans and upregulate the gene expression of collagen II but also can reduce the degradation of extracellular matrixes by decreasing the production of matrix metallopetidase-13 (MMP-13) [54–56]. The research has shown that IGF-1 exerts these functions in a dose-dependent manner [57]. Low dose of IGF-1 has a beneficial effect on bone remodeling by increasing bone formation markers in serum [58]. Higher IGF-1 levels in osteoarthritis (OA) osteoblasts could be correlated with bone sclerosis [59].
