Stromal-Cell-Derived Factor-1(SDF-1) Down-Regulates ANKH via NF-kB Promote Formation of Chondrocyte Mineralization.

Abstract

Osteoarthritis (OA) is one of the most common forms of arthritis. However, the pathogenesis of OA remains unclear. Previous studies suggested that stromal-cell-derived factor (SDF)-1 was associated with some characteristic changes in cartilage. The aim of this study is, therefore, to explore the mechanism of SDF-1 promotes chondrocyte mineralization in OA. The effect of SDF-1 was analyzed with human C-28/I2 chondrocytes. The chondrocytes were transfected with pEX-4-ANKH or siRNA and treated with related inhibitor. The chondrocytes were subjected to Alizarin red S staining, PiPer phosphate assay kit, Alkaline phosphatase staining , RT-PCR and Western blot analysis. In vitro, SDF-1 markedly promoted the mineralization of chondrocytes and suppressed the expression of ANKH, the endogenous mineralization inhibitor. ANKH overexpressed in the chondrocytes significantly decreased the levels of the mineralization in response to SDF-1 treatment. Moreover, SDF-1 promoted an increase in the expression of p-TAK1 and p-IKKβ、p-IkB、p-NF-kB p65. Furthermore, SDF-1 induced decrease in ANKH expression was blocked by IKKβVI (IkB kinase inhibitor). To conclude, SDF-1 suppresses the expression of ANKH via activating NF-kB pathway to aggravate human chondrocytes calcification, suggesting blockade of SDF-1 might be a novel therapy for treatment of OA patients.