Liqiang Zhang1, Wenjia Liu1, Jiangdong Zhao2, Xiaojie Ma3, Lin Shen3, Yongjie Zhang1, Fang Jin4, Yan Jin5. 1. MS-State Key Laboratory, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China; Institute for Tissue Engineering and Regenerative Medicine Research of Xi'an, Shaanxi 710032, People's Republic of China. 2. Department of Aerospace Biodynamics, Faculty of Aerospace Medicine, The Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China. 3. MS-State Key Laboratory, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China. 4. MS-State Key Laboratory, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China. Electronic address: jinfang@fmmu.edu.cn. 5. MS-State Key Laboratory, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China; Institute for Tissue Engineering and Regenerative Medicine Research of Xi'an, Shaanxi 710032, People's Republic of China. Electronic address: yanjin@fmmu.edu.cn.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. GENERAL SIGNIFICANCE: We describe a novel potential mechanism related to tooth movement.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. GENERAL SIGNIFICANCE: We describe a novel potential mechanism related to tooth movement.