Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg 93053, Germany.
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg 93053, Germany.
Tissue Cell. 2024 Oct;90:102522. doi: 10.1016/j.tice.2024.102522. Epub 2024 Aug 9.
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 GÖ6976, 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 GÖ6976 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 GÖ6976 and that its gene expression is likely maintained by PKC via the BMP signaling pathway. Furthermore, supplementation of osteogenic differentiation medium with sclerostin impairs GÖ6976-induced differentiation of DFCs. Our data suggest that regulation of sclerostin mediates PKC inhibition-induced mineralization of DFCs.
人牙囊细胞（DFCs）作为多能干细胞，在再生医学领域受到广泛关注，因为它们具有再生牙齿组织、牙周或退行性疾病引起的骨缺损以及治疗颅面畸形的潜力。然而，其向矿化细胞分化的分子机制仍不完全清楚。先前的研究表明，GÖ6976，一种经典蛋白激酶 C（PKC）同工型的抑制剂，可增强 DFCs 的成骨分化。增加成骨分化的可能机制是调节成骨抑制物。因此，本研究探讨了 GÖ6976 是否调节成骨分化抑制剂骨硬化蛋白（SOST），以及添加骨硬化蛋白是否会减弱 PKC 抑制剂的刺激作用。我们证明，PKC 抑制剂 GÖ6976 抑制后，骨硬化蛋白基因的表达降低，其基因表达可能通过 BMP 信号通路由 PKC 维持。此外，在成骨分化培养基中补充骨硬化蛋白会损害 GÖ6976 诱导的 DFCs 分化。我们的数据表明，骨硬化蛋白的调节介导了 PKC 抑制诱导的 DFCs 矿化。
