Role Of Leptin In Chondrogenic Progenitor Cells

Obesity contributes to the mechanical theory of OA(Osteoarthritis)pathogenesis.White adipose tissue is the main body of leptin secretion.Leptin levels are significantly positive correlation with cartilage degeneration in OA patients.However the mechanisms of leptin-induced cartilage degeneration are poorly understood.Chondrogenic progenitor cells(CPCs),which are the mesenchymalstem-like cells and have clonigenicty and stemness,are an important factor in the maintenance of cartilage homeostasis.To investigatethe effects of leptin on the differentiation and proliferation of CPCs can be helpful tounderstand the roles of leptin in the aetiology and development of OA.Pathological doses of leptin decreases the migration ability,inhibits the chondrogenic potential and increases the osteogenic potential of CPCs,suggesting leptin changes the differentiation fate of CPCs.Pathological doses of leptin induces cell cycle arrest and senescence in CPCs via p53/p21 pathway activation and Sirt1 pathway inhibition.Activation of leptin pathway(higher expression of Ob-Rb)significantly correlated with cartilage degeneration(lower level of Coll-2)and tissue senescence(higher level of p53/p21 and lower level of Sirt1)in OA patients,suggesting leptin-induced CPCs senescence contributes to development of OA.