PDL Progenitor–Mediated PDL Recovery Contributes to Orthodontic Relapse

Abstract

Periodontal ligament (PDL) is subjected to mechanical force during physiologic activities. PDL stem /: progenitor cells are the main mesenchymal stem cells in PDL. However, how PDL progenitors participate in PDL homeostasis upon and after mechanical force is largely unknown. In this study, force-triggered orthodontic tooth movement and the following relapse were used as models to demonstrate the response of PDL progenitors and their role in PDL remodeling upon and after mechanical force. Upon orthodontic force, PDL collagen on the compression side significantly degraded, showing a broken and disorganized pattern. After force withdrawal, the degraded PDL collagen recovered during the early stage of relapse. Correspondingly, increased CD90(+) PDL progenitors with suppressed expression of type I collagen (Col-I) were observed upon orthodontic force, whereas these cells accumulated at the degradation regions and regained Col-I expression after force withdrawal during early relapse. Our results further showed that compressive force altered cell morphology and repressed collagen expression in cultured PDL progenitors, which both recovered after force withdrawal. Force withdrawal-induced recovery of collagen expression in cultured PDL progenitors could be regulated by transforming growth factor-β (TGF-β), a key molecule for tissue homeostasis and extracellular matrix remodeling. More interesting, inhibiting the regained Col-I expression in CD90(+) PDL progenitors by blocking TGF-β interrupted PDL collagen recovery and partially inhibited the early relapse. These data suggest that PDL progenitors can respond to mechanical force and may process intrinsic stability to recover to original status after force withdrawal. PDL progenitors with intrinsic stability are required for PDL recovery and consequently contribute to early orthodontic relapse, which can be regulated by TGF-β signaling.

Biomechanical stress regulates mammalian tooth replacement via the integrin β1‐RUNX2‐Wnt pathway

“…Static compression was applied to DFCs using the weighted glass coverslip method (Fig T; Feng et al , ). To determine the optimum force value and loading time, we first analyzed the relative IF expression levels of RUNX2 and p‐ERK1/2 upon force loading with 1.0 g/cm 2 for 0, 1, 2, and 4 h and found that expression levels were highest at 2 h (Appendix Fig S8A–D).…”

“…To study whether the mechanical force regulated the integrin β1‐ERK1‐RUNX2‐Wnt pathway at a cellular level, we applied compressive force to DFCs using the weighted cover glass method (Feng et al , ). Briefly, a round glass cover was rinsed with PBS and then placed over an 80% confluent cell layer.…”

Mechanosensing by Gli1+ cells contributes to the orthodontic force‐induced bone remodelling

“…The cells in periodontal ligament (PDLCs), which contain fibroblasts, osteoblasts, cementoblasts, endothelial cells and stromal/stem cells, are the primary respondents to mechanical force and key factors to alveolar bone remodelling 5,6 . Given the human periodontal ligament stromal/stem cells (hPDLSCs) are obtained and cultured easily in vitro, they have been intensively evaluated to partly elucidate the mechanism of OTM 7,8 . It has been proposed that hPDLSCs respond to mechanical force including differentiating into osteoblasts under tensile stress 5 and promoting maturation of osteoclasts under compressive stress 9,10 .…”

Mechanical Force Modulates Periodontal Ligament Stem Cell Characteristics During Bone Remodeling via TRPV4

“…As the main MSCs in the PDL, PDLSCs play an important role in maintaining periodontal tissue homeostasis and alveolar bone remodeling [8][9][10]. They are mechanosensitive and respond to mechanical stimulation both in vivo and in vitro [27][28][29]. PDLSCs mediate the in ammatory process and promote osteoclastogenesis under mechanical stimulation in vivo.…”

“…Our previous studies showed that PDLSCs highly express β-2 adrenergic receptor and produce a high level of H 2 S under a static compression stimulus to increase the RANKL/OPG ratio and promote osteoclastic differentiation [19,27]. In addition, PDLSCs induce polarization of in ammatory M1 macrophages, thereby contributing to osteoclastogenesis.…”