Abstract
We investigate whether the expression of the receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) in human dental follicle cells (HDFCs) regulated by colony stimulating factor 1 (CSF-1), parathyroid hormone-related protein (PTHrP) and bone morphogenetic protein-2 (BMP-2) contributes to osteoclastogenesis. Adolescent human impacted third mandibular molars were used to separate HDFCs. These cells were incubated with PTHrP (10 ng/ml), CSF-1 (25 ng/ml), or BMP-2 (100 ng/ml) for 0.5, 1, 3, 6 and 12 h. The expression of OPG and RANKL was investigated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Two co-culture systems and tartrate-resistant acid phosphatase (TRAP) staining were used to examine osteoclast formation. Scanning electron microscopy was utilized for the resorption pit assay. RANKL and OPG were expressed innately in HDFCs. Exogenous PTHrP, CSF-1 and BMP-2 chronologically regulated the expression of RANKL and OPG in HDFCs. PTHrP and CSF-1 had similar regulative patterns leading to the up-regulated expression of RANKL and the down-regulated expression of OPG and opposite for BMP-2. The number of TRAP-positive peripheral blood mononuclear cells (PBMCs) slightly increased in contacted co-culture of HDFCs and PBMCs, whereas secreted OPG from HDFCs inhibited osteoclastogenesis in the transwell co-culture system. Contacted co-culture of HDFCs and PBMCs exhibited small and shallow resorption pits, whereas in the transwell co-culture system, secreted OPG from HDFCs reduced the resorption pits, reflecting the difference in osteoclast production. Collectively, we found a dual action of HDFCs in osteoclastogenesis; moreover, PTHrP, CSF-1 and BMP-2 might influence osteoclastogenesis by regulating the expression of RANKL and OPG in HDFCs.
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References
Beck F, Tucci J, Russell A, Senior P, Ferguson M (1995) The expression of the gene coding for parathyroid hormone-related protein (PTHrP) during tooth development in the rat. Cell Tissue Res 280:283–290
Canalis E, Economides AN, Gazzerro E (2003) Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev 24:218–235
Cotton WR, Gaines JF (1974) Unerupted dentition secondary to congenital osteopetrosis in the Osborne-Mendel rat. Exp Biol Med 146:554–561
Fujikawa Y, Quinn J, Sabokbar A, McGee J, Athanasou N (1996) The human osteoclast precursor circulates in the monocyte fraction. Endocrinology 137:4058–4560
Gorski JP, Marks SC Jr (1992) Current concepts of the biology of tooth eruption. Crit Rev Oral Biol Med 3:185–206
Hanada R, Hanada T, Sigl V, Schramek D, Penninger JM (2011) RANKL/RANK-beyond bones. J Mol Med (Berl) 89:647–656. doi:10.1007/s00109-011-0749-z
Heinrich J, Bsoul S, Barnes J, Woodruff K, Abboud S (2005) CSF-1, RANKL and OPG regulate osteoclastogenesis during murine tooth eruption. Arch Oral Biol 50:897–908
Hofbauer LC, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S (1998) Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenetic protein-2, and cytokines. Biochem Biophys Res Commun 250:776–781
Iizuka T-I, Cielinski M, Aukerman SL, Marks SC Jr (1992) The effects of colony-stimulating factor-1 on tooth eruption in the toothless (osteopetrotic) rat in relation to the critical periods for bone resorption during tooth eruption. Arch Oral Biol 37:629–636
Kitahara Y, Suda N, Kuroda T, Beck F, Hammond V, Takano Y (2002) Disturbed tooth development in parathyroid hormone-related protein (PTHrP)-gene knockout mice. Bone 30:48–56
Kitamura A, Motohashi N, Kawamoto T, Baba Y, Suzuki S, Kuroda T (2002) Tooth eruption into the newly generated bone induced by recombinant human bone morphogenetic protein-2. Cleft Palate Craniofac J 39:449–456
Liu D, Yao S, Pan F, Wise G (2005) Chronology and regulation of gene expression of RANKL in the rat dental follicle. Eur J Oral Sci 113:404–409
Liu J, Tabata M, Yamashita K, Matsumura T, Iwamoto M, Kurisu K (1998) Developmental role of PTHrP in murine molars. Eur J Oral Sci 106:143–146
Marks SC Jr, Cahill DR (1987) Regional control by the dental follicle of alterations in alveolar bone metabolism during tooth eruption. J Oral Pathol 16:164–169
Mekaapiruk K, Suda N, Hammond VE, Beck F, Kuroda T, Takano Y, Terashima T (2002) The influence of parathyroid hormone-related protein (PTHrP) on tooth-germ development and osteoclastogenesis in alveolar bone of PTHrP-knock out and wild-type mice in vitro. Arch Oral Biol 47:665–672
Myllarniemi S, Perheentupa J (1978) Oral findings in the autoimmune polyendocrinopathy-candidosis syndrome (APECS) and other forms of hypoparathyroidism. Oral Surg Oral Med Oral Pathol 45:721–729
Neves J, Salmon C, Omar N, Narvaes E, Gomes J, Novaes P (2009) Immunolocalization of CSF-1, RANKL and OPG in the enamel-related periodontium of the rat incisor and their implications for alveolar bone remodeling. Arch Oral Biol 54:651–657
Philbrick W, Wysolmerski JJ, Galbraith S, Holt E, Orloff JJ, Yang KH, Vasavada RC, Weir EC, Broadus AE, Stewart AF (1996) Defining the roles of parathyroid hormone-related protein in normal physiology. Physiol Rev 76:127–173
Philbrick WM, Dreyer BE, Nakchbandi IA, Karaplis AC (1998) Parathyroid hormone-related protein is required for tooth eruption. Proc Natl Acad Sci U S A 95:11846–11851
Simonet W, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319
Srivastava S, Toraldo G, Weitzmann MN, Cenci S, Ross FP, Pacifici R (2001) Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-κB ligand (RANKL)-induced JNK activation. J Biol Chem 276:8836–8840
Suda T, Udagawa N, Nakamura I, Miyaura C, Takahashi N (1995) Modulation of osteoclast differentiation by local factors. Bone 17:87S–91S
Wise GE (2009) Cellular and molecular basis of tooth eruption. Orthod Craniofacial Res 12:67–73. doi:10.1111/j.1601-6343.2009.01439.x
Wise G, Lin F, Zhao L (1995) Transcription and translation of CSF-1 in the dental follicle. J Dent Res 74:1551–1557
Wise G, Lumpkin S, Huang H, Zhang Q (2000) Osteoprotegerin and osteoclast differentiation factor in tooth eruption. J Dent Res 79:1937–1942
Wise G, Frazier-Bowers S, D’souza R (2002a) Cellular, molecular, and genetic determinants of tooth eruption. Crit Rev Oral Biol Med 13:323–335
Wise GE, Yao S, Zhang Q, Ren Y (2002b) Inhibition of osteoclastogenesis by the secretion of osteoprotegerin in vitro by rat dental follicle cells and its implications for tooth eruption. Arch Oral Biol 47:247–254
Wise G, Ding D, Yao S (2004) Regulation of secretion of osteoprotegerin in rat dental follicle cells. Eur J Oral Sci 112:439–444
Wise GE, Yao S, Odgren PR, Pan F (2005) CSF-1 regulation of osteoclastogenesis for tooth eruption. J Dent Res 84:837–841
Wise GE, Yao S, Henk WG (2007) Bone formation as a potential motive force of tooth eruption in the rat molar. Clin Anat 20:632–639
Wysolmerski JJ, Cormier S, Philbrick WM, Dann P, Zhang JP, Roume J, Delezoide AL, Silve C (2001) Absence of functional type 1 parathyroid hormone (PTH)/PTH-related protein receptors in humans is associated with abnormal breast development and tooth impaction. J Clin Endocrinol Metab 86:1788–1794
Yao S, Ring S, Henk WG, Wise GE (2004) In vivo expression of RANKL in the rat dental follicle as determined by laser capture microdissection. Arch Oral Biol 49:451–456
Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K (1998) Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139:1329–1337
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Haiyan Sun, Qihong Li and Yongkuan Zhang contributed equally to this work.
This study was supported by the Beijing Natural Science Foundation (no. 7122133) and the National Natural Science Foundation of China (no. 81100782).
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Sun, H., Li, Q., Zhang, Y. et al. Regulation of OPG and RANKL expressed by human dental follicle cells in osteoclastogenesis. Cell Tissue Res 362, 399–405 (2015). https://doi.org/10.1007/s00441-015-2214-8
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DOI: https://doi.org/10.1007/s00441-015-2214-8