Osteoblasts stimulate osteoclastogenesis via RANKL expression more strongly than periodontal ligament cells do in response to PGE2
Introduction
Orthodontic tooth movement occurs during sequential bone remodelling induced by therapeutic mechanical stress.1 Mechanical stress induces bone resorption on the compression side and bone formation on the tension side.2, 3, 4 On the compression side, osteoclast formation and differentiation are regulated by the balance among the receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), and macrophage colony-stimulating factor (M-CSF).5, 6 Many studies have shown that bone resorption via osteoclasts is mediated by prostaglandins, especially prostaglandin E2 (PGE2),7, 8 which is produced by periodontal ligament cells (PDLs) in response to mechanical stress in vivo9 and in vitro.7, 10, 11 PGE2 also stimulates RANKL expression.12, 13 Some studies reported that PDLs express RANKL in response to mechanical stress,7, 14 whereas another study reported that they do not.15 However, ankylosed teeth cannot be moved by therapeutic mechanical stress, suggesting that PDLs play a major role in alveolar bone resorption. Based on an immunohistochemical study, RANKL is expressed consistently around the alveolar bone surface 3 days after tooth movement.16 Consequently, PGE2 produced in response to mechanical stress in PDLs may stimulate RANKL expression directly in PDLs and in surrounding cells, such as osteoblasts in alveolar bone.
In this study, we compared the functional difference in osteoclastogenesis between human PDLs (HPDLs) and normal human osteoblasts (HOBs) on the application of PGE2 produced by HPDLs in response to mechanical stress.7, 10
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Cell cultures
The protocol for this experiment was reviewed and approved by the Nihon University Department of Dentistry Ethics Committee. HPDLs were obtained from the healthy premolars of 14 patients aged 11–50 years in the course of orthodontic treatment. HPDLs were isolated and cultured according to Somerman et al.17 The cells were cultured in α-minimum essential medium (α-MEM) supplemented with 10% foetal bovine serum (FBS), 100 U/mL penicillin-G sodium, 100 μg/mL streptomycin sulfate, and 0.25 μg/mL
Effect of compressive force on RANKL and COX-2 mRNA expression
RANKL and COX-2 expression in HPDLs in response to 24 h of compressive force (comp) are shown in Fig. 1A. Although COX-2 expression increased significantly in response to the compressive force in all 14 HPDLs compared with the non-compression controls, RANKL expression was almost undetected. Marked RANKL expression was observed in HPDLs 2, 12, and 13, but it did not depend on the compressive force (Fig. 1B).
Effect of PGE2 on RANKL, OPG, and M-CSF mRNA expression
RANKL expression in HPDLs and HOBs after a 48-h culture with 0–10−5 M PGE2 is shown in
Discussion
PGE2 is a potent osteoclast-inducing factor20, 21, 22 that is produced in PDLs in response to mechanical stress in vivo9 and in vitro.7, 10, 11 PGE2 induces RANKL expression in osteoblasts5 and HPDLs.7 RANKL has been identified as a key cytokine that regulates osteoclastogenesis and bone resorption.23 During tooth movement, alveolar bone resorption by osteoclasts is regulated by the balance among RANKL, OPG, and M-CSF.24
Some studies have reported that PDLs express RANKL in response to
Funding
Grant-in-Aid for Scientific Research (c) (22592298) and the “Strategic Research Base Development” Program for Private Universities (S1001024) from the Ministry of Education, Science, Culture, Sports, Science and Technology. A Grant from the Dental Research Centre and Sato Fund, Nihon University School of Dentistry.
Competing interests
None declared.
Ethical approval statement
The protocol for this experiment was reviewed and approved by the Nihon University Department of Dentistry and Ethics committee (Ref. no. 2).
Acknowledgments
This study was supported by a Grant-in-Aid for Scientific Research (c) (22592298) and the “Strategic Research Base Development” Program for Private Universities (S1001024) from the Ministry of Education, Science, Culture, Sports, Science and Technology, a Grant from the Dental Research Centre and Sato Fund, Nihon University School of Dentistry, and The Promotion and Mutual Aid Corporation for Private Schools of Japan.
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Bovine lactoferrin inhibits alveolar bone destruction in an orthodontic rat model with periodontitis
2021, Annals of AnatomyCitation Excerpt :Prostaglandin E2 (PGE2) is a critical osteoclast-inducing factor produced in periodontal ligament cells (PDLs) under mechanical stress both in vivo and in vitro. PGE2 up-regulates RANKL expression in PDLs (Mayahara et al., 2012), while COX-2 acts as a key rate-limiting enzyme that converts arachidonic acid to PGE2 (Li et al., 2018). During orthodontic tooth movement, osteoclastic activity mainly occurs in the pressure zone, accompanied by the up-regulation of COX-2 and PGE-2 expression, which leads to the subsequent increase in RANKL/OPG ratio and bone resorption (Inubushi et al., 2014).
Association of clinical variables and polymorphisms in RANKL, RANK, and OPG genes with external apical root resorption
2019, American Journal of Orthodontics and Dentofacial OrthopedicsCitation Excerpt :The balance of the relative concentration of RANKL, RANK, and OPG in bone becomes a determinant factor.18,19,63 Studies have revealed new functions of this triad in other diseases as well, suggesting that, in response to mechanical forces, osteocytes regulate the recruitment of osteoclasts to the site of bone resorption induced by RANKL expression in the osteoblastic cells.64,65 Pathogenic mechanisms of root resorption seem to be quite similar to those of osteoclastic bone resorption.66,67
The effect of metal ions released from different dental implant-abutment couples on osteoblast function and secretion of bone resorbing mediators
2017, Journal of DentistryCitation Excerpt :It has been shown that cobalt ions stimulate increased prostaglandin E2 (PGE2) secretion in primary human osteoblasts [26]. This was preceded by up-regulated cyclooxygenase COX-1 and COX-2 gene expression [19,26,27]. Secretion of interleukins 6 and 8 (IL-6 and IL-8) by osteoblasts in response to Ti and other experimentally derived wear particles/ions has also been previously reported [28–30].
Osteoblasts subjected to tensile force induce osteoclastic differentiation of murine macrophages in a coculture system
2015, Journal of Dental SciencesCitation Excerpt :Accumulating evidence indicates that different mechanical forces stimulate cellular messages and results through similar mechanoreceptors and intracellular biochemical cascade signaling effectors in many types of cells.11,12 Proinflammatory cytokines secreted by osteoblasts are upregulated immediately under tensile force and remain upregulated in the presence of force.13 In addition, osteoclast formation and differentiation are regulated by the balance among the receptor activators RANKL, OPG, and macrophage colony-stimulating factor.14