TY - JOUR
T1 - Inhibition of c-Jun N-terminal kinase signaling promotes osteoblastic differentiation of periodontal ligament stem cells and induces regeneration of periodontal tissues
AU - Kaneko, Hiroshi
AU - Hasegawa, Daigaku
AU - Itoyama, Tomohiro
AU - Yoshida, Shinichiro
AU - Tomokiyo, Atsushi
AU - Hamano, Sayuri
AU - Sugii, Hideki
AU - Maeda, Hidefumi
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2022/2
Y1 - 2022/2
N2 - Objectives: 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. Design: 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. Results: 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. Conclusion: 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.
AB - Objectives: 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. Design: 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. Results: 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. Conclusion: 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.
KW - JNK inhibition
KW - Osteoblastic differentiation
KW - Periodontal ligament stem cells
KW - Periodontal tissue regeneration
KW - SP600125
UR - http://www.scopus.com/inward/record.url?scp=85120917748&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85120917748&partnerID=8YFLogxK
U2 - 10.1016/j.archoralbio.2021.105323
DO - 10.1016/j.archoralbio.2021.105323
M3 - Article
C2 - 34896864
AN - SCOPUS:85120917748
SN - 0003-9969
VL - 134
JO - Archives of Oral Biology
JF - Archives of Oral Biology
M1 - 105323
ER -