Mechanical stress regulates osteogenic differentiation and RANKL/OPG ratio in periodontal ligament stem cells by the Wnt/β-catenin pathway

• Published in: Biochimica et biophysica acta 2016-10, Vol.1860 (10), p.2211-2219
• Main Authors: Zhang, Liqiang, Liu, Wenjia, Zhao, Jiangdong, Ma, Xiaojie, Shen, Lin, Zhang, Yongjie, Jin, Fang, Jin, Yan
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - genetics; Gene Expression Regulation, Developmental; Humans; Mechanical stress; Mesenchymal Stromal Cells - metabolism; Nestin - genetics; Nestin - metabolism; Orthodontic tooth movement; Osteogenesis - genetics; Osteogenic differentiation; Osteoprotegerin - biosynthesis; Osteoprotegerin - genetics; PDLSCs; Periodontal Ligament - growth & development; Periodontal Ligament - metabolism; RANK Ligand - biosynthesis; RANK Ligand - genetics; RANKL/OPG; Rats; Receptor, Platelet-Derived Growth Factor alpha - genetics; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Stress, Mechanical; Tooth Movement Techniques; Wnt Signaling Pathway - genetics; Wnt/β-catenin pathway
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2016.05.003

The balance between osteoblastic and osteoclastic activity is critical in orthodontic tooth movement (OTM). Mesenchymal stem cells (MSCs) play an important role in maintaining bone homeostasis, and periodontal ligament stem cells (PDLSCs) are tissue-specific MSCs in the periodontal ligament. However, whether PDLSCs are required for periodontal tissue remodeling during OTM is not fully understood. Here, we used PDGFRα and Nestin to trace PDLSCs during OTM in rats. We treat human PDLSCs with 100kpa static pressure for 1h or 12h in vitro, and examined the phenotypic changes and expression of RANKL and OPG in these cells. In vivo, we found that positive signals of PDGFRα and Nestin in the PDL gradually increased and then decreased on the pressure side to which pressure was applied. In vitro, the osteogenic differentiation of PDLSCs was significantly increased after force treatment for 1h relative to 12h. In contrast, the expression ratio of RANKL/OPG was reduced at 1h and significantly increased at 12h. Furthermore, we found that the Wnt/β-catenin pathway was dynamically activated in the PDL and in PDLSCs after mechanical stimulation. Importantly, the canonical Wnt pathway inhibitor DKK1 blocked the osteogenesis effect and rescued the ratio of RANKL/OPG in PDLSCs under force treatment for 1h. Our findings reveal that PDLSCs participate in OTM and that the Wnt/β-catenin pathway maintains bone homeostasis during tooth movement by regulating the balance between osteoblastic and osteoclastic activity. We describe a novel potential mechanism related to tooth movement. •Endogenous PDLSCs may reactivate during orthodontic tooth movement.•The effects of mechanical force in PDLSCs depends on the force treatment time.•The Wnt/β-catenin pathway is important in maintaining the force effects in PDLSCs.