Cyclical Tensile Force on Periodontal Ligament Cells Inhibits Osteoclastogenesis through OPG Induction

Abstract

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.

Local delivery of osteoprotegerin inhibits mechanically mediated bone modeling in orthodontic tooth movement

“…As it is not the result of tissue remodeling, the amount of movement in this phase is dependent on its biophysical limitations. During the remaining phases (days [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21], the high OPG group demonstrated almost no additional molar movement.…”

“…Compressive mechanical loading of isolated PDL cells leads to a substantial upregulation of RANKL with little change or slight increase in OPG expression which in turn increases osteoclastogenesis when loaded cells are co-cultured with peripheral bone mononuclear cells [4,5]. Also, conditioned media from osteoblasts subjected to microgravity show an increase in the RANKL/OPG ratio, which is accompanied by increased osteoclastogenesis and bone resorption in mouse bone marrow cultures when compared to cells grown at 1 g. In contrast, dynamic tensile loading upregulates OPG mRNA and concentration of OPG in conditioned medium, while having little effect on the levels of RANKL in human PDL cells [6], and conditioned media of PDL cells subjected to cyclical tensile force inhibit osteoclastogenesis [7]. Similarly, human osteoblasts demonstrate increased OPG expression but also a decrease in soluble RANKL when subjected to cyclic tensile strain [8].…”

Release from optimal compressive force suppresses osteoclast differentiation

“…Mechanical stimuli include tensile force (8,9,(11)(12)(13)(14), compressive force (7,10,(15)(16)(17), hydrostatic pressure (18), sheer stress (19,20), rotative stress (21) and others (22,23). Stimulation with tensile force using a Flexercell tension system suppresses osteoclast differentiation and fusion.…”

Mechanical stretching induces osteoprotegerin in differentiating C2C12 precursor cells through noncanonical Wnt Pathways

“…(2) The balance of RANKL and OPG is modulated by vitamin D, (3) estrogen hormones, (4) parathyroid hormone, (5) and mechanical loading. (6)(7)(8)(9) OPG also serves as a decoy receptor for tumor necrosis factor (TNF)-related apoptotic-inducing ligand (TRAIL) and thus acts to increase cell survival by blocking the proapoptotic effects of this ligand. (10) Secretion of OPG by a variety of tumor cells is a potential mechanism by which these cells could become resistant to TRAIL-induced apoptosis.…”