Destruction of cementum and alveolar bone is the main causative event for the exfoliation of teeth as a consequence of periodontitis. Prostaglandin E2 (PGE2) and PGE receptor subtypes (EPs) play an important role in modulating osteoblast-mediated osteoclastogenesis; however, no information is available on the role of PGE2 and EPs in regulating cementoblast-mediated cementoclastogenesis. We hypothesized that the PGE2-EPs pathway also regulates cementoblasts’ ability to activate cementoclasts. For these studies, OCCM-30 cells (a mouse cementoblast cell line) were exposed to PGE2 and specific EP agonists. PGE2 (100 ng/mL) and EP4 agonist (1 μM) up-regulated RANKL and IL-6 mRNA levels, while they down-regulated OPG mRNA expression. The EP4 antagonist (1 μM) eliminated these effects of PGE2. PGE2 treatment of co-cultures of OCCM-30 cells with bone marrow cells induced TRAP-positive cells via the EP4 pathway. These findings suggest that PGE2 promotes cementoblast-mediated cementoclastogenesis by regulating the expression of RANKL and OPG via the EP4 pathway.
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References
1.
Akatsu T, Takahashi N, Debari K, Morita I, Murota S, Nagata N, et al. -1989-. Prostaglandins promote osteoclast-like cell formation by a mechanism involving cyclic adenosine 3′, 5′-monophosphate in mouse bone marrow cell cultures. J Bone Miner Res4:29–35.
2.
Boabaid F, Berry JE, Koh AJ, Somerman MJ, McCauley LK -2004-. The role of parathyroid hormone-related protein in the regulation of osteoclastogenesis by cementoblasts. J Periodontol75:1247–1254.
3.
Carranza FA Jr, Bernard GW -2002-. Clinical periodontology. In: The tooth-supporting structures. Newman MG, Takei H, Carranza FA, eds. Carranza’s clinical periodontology. 9th ed. Philadelphia: W.B. Saunders, pp. 36–57.
4.
Chen Y, Hughes-Fulford M -2000-. Prostaglandin E2 and the protein kinase A pathway mediate arachidonic acid induction of c-fos in human prostate cancer cells. Br J Cancer82:2000–2006.
5.
Choi BK, Moon SY, Cha JH, Kim KW, Yoo YJ -2005-. Prostaglandin E-2- is a main mediator in receptor activator of nuclear factor-kappaB ligand-dependent osteoclastogenesis induced by Porphyromonas gingivalis, Treponema denticola, and Treponema socranskii. J Periodontol76:813–820.
6.
Coleman RA, Smith WL, Narumiya S -1994-. International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev46:205–229.
7.
Collins DA, Chambers TJ -1991-. Effect of prostaglandins E1, E2 and F2alpha on osteoclast formation in mouse bone marrow cultures. J Bone Miner Res6:157–164.
8.
D’Errico JA, Ouyang H, Berry JE, Macneil RL, Strayhorn C, Imperiale MJ, et al. -1999-. Immortalized cementoblasts and periodontal ligament cells in culture. Bone25:39–47.
9.
D’Errico JA, Berry JE, Ouyang H, Strayhorn C, Windle JJ, Somerman MJ -2000-. Employing a transgenic animal model to obtain cementoblasts in vitro. J Periodontol71:63–72.
10.
Freeman E -1994-. Periodontium. In: Oral histology: development, structure and function. Ten Cate AR, editor. St. Louis: Mosby, pp. 276–312.
11.
Fujino H, West KA, Regan JW -2002-. Phosphorylation of glycogen synthase kinase-3 and stimulation of T-cell factor signaling following activation of EP2 and EP4 prostanoid receptors by prostaglandin E2. J Biol Chem277:2614–2619.
12.
Klein DC, Raisz LG -1970-. Prostaglandins: stimulation of bone resorption in tissue culture. Endocrinology86:1436–1440.
13.
Lee SK, Lorenzo JA -2002-. Regulation of receptor activator of nuclear factor-kappa B ligand and osteoprotegerin mRNA expression by parathyroid hormone is predominantly mediated by the protein kinase a pathway in murine bone marrow cultures. Bone31:252–259.
14.
Li X, Pilbeam CC, Pan L, Breyer RM, Raisz LG -2002-. Effects of prostaglandin E2 on gene expression in primary osteoblastic cells from prostaglandin receptor knockout mice. Bone30:567–573.
15.
Liu XH, Kirschenbaum A, Yao S, Levine AC -2005-. Cross-talk between the interleukin-6 and prostaglandin E-2- signaling systems results in enhancement of osteoclastogenesis through effects on the osteoprotegerin/receptor activator of nuclear factor-{kappa}B -RANK- ligand/RANK system. Endocrinology146:1991–1998.
16.
Miyauchi M, Hiraoka M, Oka H, Sato S, Kudo Y, Ogawa I, et al. -2004-. Immunolocalization of COX-1 and COX-2 in the rat molar periodontal tissue after topical application of lipopolysaccharide. Arch Oral Biol49:739–746.
17.
Namba T, Sugimoto Y, Negishi M, Irie A, Ushikubi F, Kakizuka A, et al. -1993-. Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP3 determines G-protein specificity. Nature365:166–170.
18.
Narumiya S, Sugimoto Y, Ushikubi F -1999-. Prostanoid receptors: structures, properties, and functions. Physiol Rev79:1193–1226.
19.
Negishi M, Sugimoto Y, Ichikawa A -1995-. Molecular mechanism of diverse actions of prostanoid receptors. Biochem Biophys Acta1259:109–119.
20.
Raisz LG -1982-. Prostaglandins and skeletal metabolism. In: Prostaglandins. Lee JB, editor. New York: Elsevier, pp. 351–372.
21.
Raisz LG, Vanderhoek JY, Simmons HA, Kream BE, Nicolaou KC -1979-. Prostaglandin synthesis by fetal rat bone in vitro: evidence for a role of prostacyclin. Prostaglandins17:905–914.
22.
Sakuma Y, Tanaka K, Suda M, Komatsu Y, Yasoda A, Miura M, et al. -2000-. Impaired bone resorption by lipopolysaccharide in vivo in mice deficient in the prostaglandin E receptor EP4 subtype. Infect Immun68:6819–6825.
23.
Shinar DM, Rodan GA -1990-. Biphasic effects of transforming growth factor-beta on the production of osteoclast-like cells in mouse bone marrow cultures: the role of prostaglandins in the generation of these cells. Endocrinology126:3153–3158.
24.
Suda K, Udagawa N, Sato N, Takami M, Itoh K, Woo JT, et al. -2004-. Suppression of osteoprotegerin expression by prostaglandin E2 is crucially involved in lipopolysaccharide-induced osteoclast formation. J Immunol172:2504–2510.
25.
Suzawa T, Miyaura C, Inada M, Maruyama T, Sugimoto Y, Ushikubi F, et al. -2000-. The role of prostaglandin E receptor subtypes -EP1, EP2, EP3, and EP4- in bone resorption: an analysis using specific agonists for the respective EPs. Endocrinology141:1554–1559.
26.
Takayama K, Sukhova GK, Chin MT, Libby P -2006-. A novel prostaglandin E receptor 4-associated protein participates in antiinflammatory signaling. Circ Res98:499–504.
27.
Wani MR, Fuller K, Kim NS, Choi Y, Chambers T -1999-. Prostaglandin E2 cooperates with TRANCE in osteoclast induction from hemopoietic precursors: synergistic activation of differentiation, cell spreading, and fusion. Endocrinology140:1927–1935.
28.
Yokota K, Kusaka M, Ohshima T, Yamamoto S, Kurihara N, Yoshino T, et al. -1986-. Stimulation of prostaglandin E2 synthesis in cloned osteoblastic cells of mouse -MC3T3-E1- by epidermal growth factor. J Biol Chem261:15410–15415.
