Cyclical tensile force on periodontal ligament cells inhibits osteoclastogenesis through OPG induction.
The periodontal ligament (PDL) maintains homeostasis of periodontal tissue under mechanical tensile-loading caused by mastication. Occlusal load inhibits atrophic alveolar bone resorption. Previously, we discovered that continuous compressive force on PDL cells induced osteoclastogenesis-supporting activity, with up-regulation of RANKL. We hypothesized that, unlike compression, cyclical tensile force up-regulates OPG expression in PDL cells via TGF-beta up-regulation, and does not induce osteoclastogenesis-supporting activity. PDL cells were mechanically stimulated by cyclical tensile force in vitro. The conditioned media of PDL cells that had been subjected to cyclical tensile force inhibited osteoclastogenesis. Cyclical tensile force up-regulated not only RANKL mRNA expression, but also OPG mRNA expression in PDL cells. Tensile force up-regulated TGF-beta expression in PDL cells as well. Administration of neutralizing antibodies to TGF-beta inhibited OPG up-regulation under cyclical tensile-force stimulation in a dose-dependent manner. Additionally, the osteoclastogenesis-inhibitory effect of the conditioned media of PDL cells under cyclical tensile force was partially rescued by the administration of TGF-beta neutralizing antibodies. In conclusion, tensile force inhibited the osteoclastogenesis-supporting activity of PDL cells by inducing the up-regulation of OPG via TGF-beta stimulation.
Kanzaki
H
H
Division of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Tohoku University, Sendai, Japan. kanzaki@mail.tains.tohoku.ac.jp
Chiba
M
M
Sato
A
A
Miyagawa
A
A
Arai
K
K
Nukatsuka
S
S
Mitani
H
H
D000328:Adult; D001732:Bite Force; D016723:Bone Remodeling / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003799:Dental Stress Analysis; D006023:Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007963:Leukocytes, Mononuclear; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D053244:Osteoprotegerin; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013718:Tensile Strength; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D015854:Up-Regulation
D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D016212:Transforming Growth Factor beta