Vitamin D Inhibition of TRPV5 Expression During Osteoclast Differentiation

BACKGROUND: Vitamin D is an important steroid that can regulate bone metabolism including osteoclast (OC) differentiation. Transient receptor potential cation channel subfamily V member 5 (TRPV5), is a calcium channel protein involved in OC differentiation. However, the impact of vitamin D on TRPV5 expression during OC differentiation is not clear. OBJECTIVES: To determine if 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3)) regulates the expression of TRPV5 during OC differentiation. METHODS: Bone marrow mononuclear macrophage (BMMs) were induced to differentiate into OC with or without treatment with 10 nM 1,25(OH)(2)D(3). The expression levels of vitamin D receptor (VDR) and TRPV5 were examined. The expression of several OC markers, including tartrate resistant acid phosphatase (TRAP), carbonic anhydrase II (Ca II), cathepsin K (CTSK), and vacuolar-type H(+)-ATPase (V-ATPase) were also detected. RESULTS: We found that the VDR was expressed in murine bone marrow-derived macrophages at the early stage of OC differentiation. TRPV5 expression was increased during OC differentiation, which was down-regulated by 1,25(OH)(2)D(3) after a prolonged exposure. The 1,25(OH)(2)D(3) and TRPV5 inhibitors inhibited OC differentiation. CONCLUSIONS: 1,25(OH)(2)D(3) can inhibit TRPV5 expression as well as TRPV5 inhibitors during OC differentiation. This suggests that 1,25(OH)(2)D(3) may suppress OC differentiation by inhibiting TRPV5 expression.