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.
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References
1.
Basdra EK, Komposch G (1997). Osteoblast-like properties of human periodontal ligament cells: an in vitro analysis. Eur J Orthod19:615–621.
2.
Bellows CG, Melcher AH, Aubin JE (1982). Association between tension and orientation of periodontal ligament fibroblasts and exogenous collagen fibres in collagen gels in vitro. J Cell Sci58:125–138.
3.
Chenu C, Pfeilschifter J, Mundy GR, Roodman GD (1988). Transforming growth factor beta inhibits formation of osteoclast-like cells in long-term human marrow cultures. Proc Natl Acad Sci USA85:5683–5687.
4.
Cohn SA (1965). Disuse atrophy of the periodontium in mice. Arch Oral Biol10:909–919.
5.
Cohn SA (1966). Disuse atrophy of the periodontium in mice following partial loss of function. Arch Oral Biol11:95–105.
6.
Davidovitch Z, Nicolay OF, Ngan PW, Shanfeld JL (1988). Neurotransmitters, cytokines, and the control of alveolar bone remodeling in orthodontics. Dent Clin North Am32:411–435.
7.
Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL (2000). The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res15:2–12.
8.
Horowitz MC, Xi Y, Wilson K, Kacena MA (2001). Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands. Cytokine Growth Factor Rev12:9–18.
9.
Ishida A, Fujita N, Kitazawa R, Tsuruo T (2002). Transforming growth factor-beta induces expression of receptor activator of NF-kappa B ligand in vascular endothelial cells derived from bone. J Biol Chem277:26217–26224.
10.
Ishida S, Kinoshita T, Sugawara N, Yamashita T, Koike K (2003). Serum inhibitors for human mast cell growth: possible role of retinol. Allergy58:1044–1052.
11.
Kaneda T, Nojima T, Nakagawa M, Ogasawara A, Kaneko H, Sato T, et al. (2000). Endogenous production of TGF-beta is essential for osteoclastogenesis induced by a combination of receptor activator of NF-kappa B ligand and macrophage-colony-stimulating factor. J Immunol165:4254–4263.
12.
Kanzaki H, Chiba M, Shimizu Y, Mitani H (2002). Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor kappaB ligand up-regulation via prostaglandin E2 synthesis. J Bone Miner Res17:210–220.
13.
Karsdal MA, Hjorth P, Henriksen K, Kirkegaard T, Nielsen KL, Lou H, et al. (2003). Transforming growth factor-beta controls human osteoclastogenesis through the p38 MAPK and regulation of RANK expression. J Biol Chem278:44975–44987.
14.
Kitamura S, Maeshima Y, Sugaya T, Sugiyama H, Yamasaki Y, Makino H (2003). Transforming growth factor-beta 1 induces vascular endothelial growth factor expression in murine proximal tubular epithelial cells. Nephron Exp Nephrol95:e79–e86.
15.
Koseki T, Gao Y, Okahashi N, Murase Y, Tsujisawa T, Sato T, et al. (2002). Role of TGF-beta family in osteoclastogenesis induced by RANKL. Cell Signal14:31–36.
16.
Lekic P, McCulloch CA (1996). Periodontal ligament cell population: the central role of fibroblasts in creating a unique tissue. Anat Rec245:327–341.
17.
Matsuda N, Morita N, Matsuda K, Watanabe M (1998). Proliferation and differentiation of human osteoblastic cells associated with differential activation of MAP kinases in response to epidermal growth factor, hypoxia, and mechanical stress in vitro. Biochem Biophys Res Commun249:350–354.
18.
Murakami T, Yamamoto M, Ono K, Nishikawa M, Nagata N, Motoyoshi K, et al. (1998). Transforming growth factor-beta1 increases mRNA levels of osteoclastogenesis inhibitory factor in osteoblastic/stromal cells and inhibits the survival of murine osteoclast-like cells. Biochem Biophys Res Commun252:747–752.
19.
Quinn JM, Itoh K, Udagawa N, Hausler K, Yasuda H, Shima N, et al. (2001). Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions. J Bone Miner Res16:1787–1794.
20.
Saito M, Saito S, Ngan PW, Shanfeld J, Davidovitch Z (1991). Interleukin 1 beta and prostaglandin E are involved in the response of periodontal cells to mechanical stress in vivo and in vitro. Am J Orthod Dentofacial Orthop99:226–240.
21.
Shimizu N, Yamaguchi M, Goseki T, Ozawa Y, Saito K, Takiguchi H, et al. (1994). Cyclic-tension force stimulates interleukin-1 beta production by human periodontal ligament cells. J Periodontal Res29:328–333.
22.
Takai H, Kanematsu M, Yano K, Tsuda E, Higashio K, Ikeda K, et al. (1998). Transforming growth factor-beta stimulates the production of osteoprotegerin/osteoclastogenesis inhibitory factor by bone marrow stromal cells. J Biol Chem273:27091–27096.
Tsuji K, Uno K, Zhang GX, Tamura M (2004). Periodontal ligament cells under intermittent tensile stress regulate mRNA expression of osteoprotegerin and tissue inhibitor of matrix metalloprotease −1 and −2. J Bone Miner Metab22:94–103.
25.
Udagawa N (2002). Mechanisms involved in bone resorption. Biogerontology3:79–83.
26.
Wang R, Zhang L, Zhang X, Moreno J, Celluzzi C, Tondravi M, et al. (2002). Regulation of activation-induced receptor activator of NF-kappaB ligand (RANKL) expression in T cells. Eur J Immunol32:1090–1098.
27.
Weitzmann MN, Cenci S, Haug J, Brown C, DiPersio J, Pacifici R (2000). B lymphocytes inhibit human osteoclastogenesis by secretion of TGFbeta. J Cell Biochem78:318–324.
28.
Yamaguchi M, Shimizu N, Goseki T, Shibata Y, Takiguchi H, Iwasawa T, et al. (1994). Effect of different magnitudes of tension force on prostaglandin E2 production by human periodontal ligament cells. Arch Oral Biol39:877–884.
29.
Yoshino H, Morita I, Murota SI, Ishikawa I (2003). Mechanical stress induces production of angiogenic regulators in cultured human gingival and periodontal ligament fibroblasts. J Periodontal Res38:405–410.
