Mechanical force modulates periodontal ligament stem cell characteristics during bone remodelling via TRPV4

• Published in: Cell proliferation Vol. 53; no. 10; pp. e12912 - n/a
• Main Authors: Jin, Shan‐Shan, He, Dan‐Qing, Wang, Yu, Zhang, Ting, Yu, Hua‐Jie, Li, Zi‐Xin, Zhu, Li‐Sha, Zhou, Yan‐Heng, Liu, Yan
• Format: Journal Article
• Language: English
• Published: Chichester John Wiley & Sons, Inc 01-10-2020; John Wiley and Sons Inc
• Subjects: Acids; Alveolar bone; Animal models; Antibodies; Biomedical materials; Bone remodeling; Cell differentiation; Cell fate; Cell growth; Cytokines; Differentiation; Immunoregulation; Inflammation; Ions; Leukocyte migration; Ligaments; Macrophages; Mechanical loading; Medical research; Mesenchymal stem cells; Mesenchyme; Original; Osteoclastogenesis; Osteoprotegerin; Periodontal ligament; Phosphatase; Signal transduction; Signaling; Stem cell transplantation; Stem cells; Teeth; TRANCE protein; Western blotting
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/cpr.12912

Objectives
Mechanical force plays an important role in modulating stem cell fate and behaviours. However, how periodontal ligament stem cells (PDLSCs) perceive mechanical stimulus and transfer it into biological signals, and thereby promote alveolar bone remodelling, is unclear.
Materials and Methods
An animal model of force‐induced tooth movement and a compressive force in vitro was used. After force application, tooth movement distance, mesenchymal stem cell and osteoclast number, and proinflammatory cytokine expression were detected in periodontal tissues. Then, rat primary PDLSCs with or without force loading were isolated, and their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation and immunoregulatory properties were evaluated. Under compressive force in vitro, the effects of the ERK signalling pathway on PDLSC characteristics were evaluated by Western blotting.
Results
Mechanical force in vivo induced PDLSC proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation; the force‐stimulated PDLSCs showed greater clonogenicity and proliferation, reduced differentiation ability, improved induction of macrophage migration, osteoclast differentiation and proinflammatory factor expression. The biological changes induced by mechanical force could be partially suppressed by TRPV4 inhibition. Mechanistically, force‐induced activation of TRPV4 in PDLSCs regulated osteoclast differentiation by affecting the RANKL/OPG system via ERK signalling.
Conclusions
Taken together, we show here that TRPV4 activation in PDLSCs under mechanical force contributes to changing their stem cell characteristics and modulates bone remodelling during tooth movement.
Mechanical force in vivo induced periodontal ligament stem cell proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation. The activation of TRPV4 in PDLSCs under mechanical force contributes to the changes in their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation, and immunoregulation and modulates bone remodelling during tooth movement.