The effect of five osteotropic factors on osteoprotegerin mRNA expression in gingival fibroblasts
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Purpose: Osteoprotegerin (OPG) is a secreted glycoprotein and a member of the tumor necrosis factor (TNF) receptor family that inhibits bone resorption by suppressing osteoclastogenesis. Gingival fibroblasts (GF) play a role in periodontal disease progression, and the purpose of this experiment was to evaluate influence of osteotropic factors on the expression of osteoprotegerin mRNA in these cells. Materials and Methods: In this experiment, the influence of osteoclastogenic factors, interleukin-1 beta (IL-1β), TNF-α, prostanglandin E2 (PGE2). parathyroid hormone (PTH) and 1α, 25-dihydroxyvitamin D3 on the expression of osteoprotegerin mRNA in GF was studied by Northern blot hybridization. Results: As expected, PGE2 tended to inhibit OPG levels and this was most prominent at 24 hours of culture with 10-7M of PGE2. TNF-α at 10ng/ml and also at 25ng/ml decreased OPG levels to almost 30% of the control at 24 hours. This contrasts with reports of increased OPG levels from osteoblast/stromal cells and gingival fibroblasts stimulated by TNF-α. Decrease of OPG levels with PGE2 and TNF-αsuggests a pathway whereby these mediators exert their resorptive effects. However, OPG levels were increased almost 3-fold at 24 hours with IL-1β(1 to 15ng/ml) and increased 1.4 fold with 24-hour treatment of 10-7M PTH. Conclusion: Increase of OPG levels suggests that these ‘osteoclastogenic’ factors act in more complex ways and may act to inhibit bone resorption in inflammatory periodontitis. This result supports the role of OPG as a negative feedback mechanism in osteoclastic activity. (J Korean Acad Periodontol 2008;38:395-404)
Abstract
Purpose: Osteoprotegerin (OPG) is a secreted glycoprotein and a member of the tumor necrosis factor (TNF) receptor family that inhibits bone resorption by suppressing osteoclastogenesis. Gingival fibroblasts (GF) play a role in periodontal disease progression, and the purpose of this experiment was to evaluate influence of osteotropic factors on the expression of osteoprotegerin mRNA in these cells. Materials and Methods: In this experiment, the influence of osteoclastogenic factors, interleukin-1 beta (IL-1β), TNF-α, prostanglandin E2 (PGE2). parathyroid hormone (PTH) and 1α, 25-dihydroxyvitamin D3 on the expression of osteoprotegerin mRNA in GF was studied by Northern blot hybridization. Results: As expected, PGE2 tended to inhibit OPG levels and this was most prominent at 24 hours of culture with 10-7M of PGE2. TNF-α at 10ng/ml and also at 25ng/ml decreased OPG levels to almost 30% of the control at 24 hours. This contrasts with reports of increased OPG levels from osteoblast/stromal cells and gingival fibroblasts stimulated by TNF-α. Decrease of OPG levels with PGE2 and TNF-αsuggests a pathway whereby these mediators exert their resorptive effects. However, OPG levels were increased almost 3-fold at 24 hours with IL-1β(1 to 15ng/ml) and increased 1.4 fold with 24-hour treatment of 10-7M PTH. Conclusion: Increase of OPG levels suggests that these ‘osteoclastogenic’ factors act in more complex ways and may act to inhibit bone resorption in inflammatory periodontitis. This result supports the role of OPG as a negative feedback mechanism in osteoclastic activity. (J Korean Acad Periodontol 2008;38:395-404)
참고문헌 (38)
- Udagawa N, "The bone marrow-derived stromal cell lines MC3T3-G2", PA6 and ST2 support osteoclast-like cell differentiation in cocultures with mouse spleen cells, 1989, pp.125, 1805~1813
- Yasuda H, "Osteoclast differentiation factor is a ligand for osteoprotegerin", osteoclastogenesis inhibitory factor and is identical to TRANCE, Proc Natl Acad Scie USA, pp.1997, 95[DOI]
- Anderson D, "A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell fuction", Nature, 390, pp.175~179 (1997)
- Lacey DL, "Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation", Cell, 93, pp.165~176 (1998)
- Wong B, "TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells", J Biol Chem, 272, pp.25190~25194 (1997)
- Takayanagi T, "Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems", Nature Reviews Immunology, 7, pp.292~305 (2007)
- Nakagawa N, "RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis", Biochem Biophys Res Commun, 253, pp.395~400 (1998)
- Yamashita T, "NF-κB p50 and p52 Regulate Receptor Activator of NF-κB Ligand (RANKL) and Tumor Necrosis Factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1", J Biol Chem, 282, pp.18245~18253 (2007)
- Simonet WS, "Osteoprotegerin: A novel secreted protein involved in the regulation of bone density", Cell, 89, pp.309~319 (1997)
- Hofbauer LC, "Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis", Endocrinology, 140, pp.4382~4389 (1999)
- Hofbauer LC, "Clinical Implications of the Osteoprotegerin", RANKL, JAMA, pp.2004, 292[DOI]
- Theoleyre S, "The molecular triad OPG", RANK, Cytokine & Growth Factor Reviews, pp.2004, 15[DOI]
- Sakata M, "Expression of osteoprotegerin (osteoclastogenesis inhibitory factor) in cultures of human dental mesenchymal cells and epithelial cells", J Bone Min Res, 14, pp.1486~1492 (1999)
- Mundy GR, "Inflammatory mediators and the destruction of bone", J Periodont Res, 26, pp.213~217 (1991)
- Yasuda H, "Identity of osteoclastogenesis inhibitory factor(OCIF) and osteoprotegerin(OPG); A mechanism by which OPG", OCIF inhibits osteoclastogenesis in vitro, 1998, pp.139, 1329~1337
- Rani SCS, "Dental cells express factors that regulate bone resorption", Molecular Cell Biol Res Comm, 3, pp.145~152 (2000)
- Wada N, "Periodontal ligamental cells secrete the factor that inhibits osteoclastic differentiation and function: the factor is osteoprotegerin", osteoclastogenesis inhibitory factor, 2001, pp.36, 56~63
- Teng YTA, "Functional T-cell immunity and osteoprotegerin control alveolar bone destruction in periodontal infection", J Clin Invest, 106, pp.R59~R67 (2000)
- Tokoro Y, "IL-1beta mRNA as the predominant inflammatory cytokine transcript:correlation with inflammatory cell infiltration into human gingival", J Oral Pathol Med, 25, pp.225~231 (1996)
- Stashenko P, "Synergistic interactions between interleukin-1, tumor necrosis factor and lymphotoxin in bone resorption", J Immunol, 138, pp.1464~1468 (1987)
- Matsuki Y, "Localization of interleukin-1 mRNA expressing macrophages in human inflamed gingiva and IL-1 activity in gingival crevicular fluid", J Periodontal Res, 28, pp.35~42 (1993)
- Koide M, "In vivo administration of IL-1 beta accelerates silk ligature-induced alveolar bone loss", J Oral Pathol Med, 24, pp.420~434 (1995)
- Nakashima T, "Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kappaB ligand: modulation of the expression by osteotropic factors and cytokines", Biochem Biophys Res Commun, 275, pp.768~775 (2000)
- Hofbauer LC, "Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenetic protein-2 and cytokines", Biochem Biophys Res Commun, 250, pp.776~781 (1998)
- O'Brien EA, "Osteoprotegerin is produced when prostaglandin synthesis is inhibited causing osteoclasts to detach from the surface of mouse parietal bone and attach to the endocranial membrane", Bone, 28, pp.208~214 (2001)
- Brandstrom H, "Regulation of osteoprotegerin secretion from primary cultures of human bone marrow stromal cells", Biochem Biophys Res Commun, 280, pp.831~835 (2001)
- Choi BK, "Prostaglandin E2 is a main mediator in receptor activator of nuclear factor-kappaB ligand-dependent osteoclastogenesis induced by Porphyromonas gingivalis, Treponema denticola, and Treponema socranskii", J Periodontol, 76, pp.813~820 (2005)
- Ogata Y, "Comparison of the characteristics of human gingival fibroblasts and periodontal ligament cells", J Periodontol, 66, pp.1025~1031 (1995)
- Horwood NJ, "Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells", Endocrinology, 139, pp.4743~4746 (1998)
- Wada N, "Lipopolysaccharide stimulates expression of osteoprotegerin and receptor activator of NF-kappa B ligand in periodontal ligament fibroblasts through the induction of interleukin-1 beta and tumor necrosis factor-alpha", Bone, 35, pp.629~635 (2004)
- Quinn JM, "Fibroblastic stromal cells express receptor activator of NF-B ligand and support osteoclast differentiation", J Bone Miner Res, 15, pp.1459~1466 (2000)
- Huang L, "Gene expression of osteoprotegerin ligand, osteoprotegerin, and receptor activator of NF-kappaB in giant cell tumor of bone: possible involvement in tumor cell-induced osteoclast-like cell formation", Am J Pathol, 156, pp.761~767 (2000)
- Suda T, "Vitamin D and Bone", J Cell Biochem, 88, pp.259~266 (2003)
- Hofbauer LC, "The role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in the pathogenesis and treatment of metabolic bone diseases", J Clin Endocrinol Metab, 85, pp.2355~2363 (2000)
- Lories RJ, "Osteoprotegerin and osteoprotegerin-ligand balance: a new paradigm in bone metabolism providing new therapeutic targets", Clin Rheumatol, 20, pp.3~9 (2001)
- Bekker PJ, "The effect of a single dose of osteoprotegerin in postmenopausal women", J Bone Miner Res, 16, pp.348~360 (2001)
- Bekker PJ, "The effect of a single dose of osteoprotegerin in postmenopausal women", J Bone Mineral Res, 16, pp.348~360 (2001)
- Cohen SB, "Denosumab treatment effects on structural damage, I. bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial", Arthritis Rheum, 59, pp.1299~1309 (2008)
