Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Division of Endodontology, Kyushu University Hospital, Kyushu University, Fukuoka, Japan.
Arch Oral Biol. 2022 Feb;134:105323. doi: 10.1016/j.archoralbio.2021.105323. Epub 2021 Nov 26.
Few clinical treatments to regenerate periodontal tissue lost due to severe endodontic and periodontal disease have yet been developed. Therefore, the development of new treatment methods for the regeneration of periodontal tissue is expected. The purpose of this study was to investigate the effects of a c-Jun N-terminal kinase (JNK) inhibitor, SP600125, on the osteoblastic differentiation of periodontal ligament stem cells (PDLSCs) in vitro, and the function of SP600125 on the regeneration of alveolar bone in vivo.
Alizarin red S staining, quantitative RT-PCR, and western blotting analysis was performed to determine whether SP600125 affects osteoblastic differentiation of human PDLSCs (HPDLSCs) and bone-related intracellular signaling. The effect of SP600125 on the regeneration of alveolar bone was assessed by using a rat periodontal defect model. The healing of periodontal defects was evaluated using micro-CT scans and histological analysis.
SP600125 promoted the osteoblastic differentiation such as Alizarin red S-positive mineralized nodule formation and the expression of osteoblast-related genes in HPDLSCs under osteogenic conditions. In addition, this inhibitor upregulated the BMP2 expression and the phosphorylation of Smad1/5/8 in HPDLSCs under the same conditions. The inhibition of Smad1/5/8 signaling by LDN193189 suppressed the SP600125-induced osteoblastic differentiation of HPDLSCs. Furthermore, the application of SP600125 promoted the regeneration of not only alveolar bone but also PDL tissue in periodontal defects.
This study suggested that inhibition of JNK signaling promotes the osteoblastic differentiation of HPDLSCs through BMP2-Smad1/5/8 signaling, leading to the regeneration of periodontal tissues such as alveolar bone and PDL tissue.
由于严重的牙髓病和牙周病导致牙周组织丧失，目前很少有临床治疗方法可以对此进行修复。因此，人们期望开发新的牙周组织再生治疗方法。本研究旨在探讨 c-Jun N 末端激酶（JNK）抑制剂 SP600125 对体外牙周膜干细胞（PDLSCs）成骨分化的影响，以及 SP600125 对体内牙槽骨再生的作用。
通过茜素红 S 染色、定量 RT-PCR 和 Western blot 分析，确定 SP600125 是否影响人牙周膜干细胞（HPDLSCs）的成骨分化及与骨相关的细胞内信号。采用大鼠牙周缺损模型评估 SP600125 对牙槽骨再生的影响。使用微 CT 扫描和组织学分析评估牙周缺损的愈合情况。
SP600125 可促进 HPDLSCs 在成骨条件下形成茜素红 S 阳性矿化结节和骨相关基因的表达，从而促进其成骨分化。此外，该抑制剂在相同条件下还可上调 BMP2 的表达和 Smad1/5/8 的磷酸化。LDN193189 抑制 Smad1/5/8 信号通路可抑制 SP600125 诱导的 HPDLSCs 成骨分化。此外，SP600125 的应用不仅促进了牙槽骨的再生，还促进了牙周缺损中牙周膜组织的再生。
本研究表明，JNK 信号通路的抑制通过 BMP2-Smad1/5/8 信号通路促进 HPDLSCs 的成骨分化，从而促进牙槽骨和牙周膜组织等牙周组织的再生。
