The Effects of Leptin on the Proliferation and Differentiation of Primary Chondrocytes in Vitro and Cartilage Regeneration in Vivo.

Patients with cartilage damage have various discomforts, including pain, clicks, deformities, and dysfunction. Chondrocytes are a crucial component of cartilage restoration; however, their limited proliferative ability and degenerative specificity dramatically reduce their effectiveness. In the present study, the effects of leptin on chondrocyte proliferation, chondrogenic and secretion marker gene expression, and chondrocyte cartilage matrix component secretion were evaluated in vitro. The roles of the mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) signaling pathways in these processes were also investigated. More importantly, a leptin sustained release system was developed using a hydrogel with calcium alginate microspheres and was transplanted into cartilage defects in rabbit femurs to analyze the effect of leptin on promoting cartilage restoration. The results showed that leptin promoted cell proliferation and chondrocyte gene expression in a dose-dependent manner, and a concentration of 100 ng/mL leptin had the greatest effect. The activation of the P38 and AKT signaling pathways might be responsible for these effects. An improved in vivo restoration outcome was observed in the leptin sustained release group compared with the control group. These results suggest that leptin could be used as a suitable drug for cartilage restoration.