Sclerostin inhibits Protein kinase C inhibitor GO<spacing diaeresis>6976 induced osteogenic differentiation of dental follicle cells

Human dental follicle cells (DFCs) as multipotent stem cells are currently investigated within the field of regenerative medicine considering their potential for the regeneration of dental tissues, bone defects caused by periodontal or degenerative diseases and the treatment of craniofacial disorders. However, molecular mechanisms of the differentiation into mineralizing cells are still inadequately understood. Previous studies have shown that GO<spacing diaeresis>6976, an inhibitor of classical isoforms of protein kinase C (PKC), enhanced ostogenic differentiation of DFCs. A possible mechanism for increased osteogenic differentiation could be the regulation of ossification inhibitors. This study therefore investigated whether the osteogenic differentiation inhibitor sclerostin (SOST) is regulated by GO<spacing diaeresis>6976 and whether the addition of sclerostin attenuates the stimulating effect of the PKC inhibitor. We demonstrated that the expression of the sclerostin gene decreased after PKC inhibition by GO<spacing diaeresis>6976 and that its gene expression is likely maintained by PKC via the BMP signaling pathway. Furthermore, supplementation of osteogenic differentiation medium with sclerostin impairs GO<spacing diaeresis>6976-induced differentiation of DFCs. Our data suggest that regulation of sclerostin mediates PKC inhibition-induced mineralization of DFCs.