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Bone morphogenetic protein 2 enhances mouse osteoclast differentiation via increased levels of receptor activator of NF-κB ligand expression in osteoblasts

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Abstract

1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] induces osteoclast formation via induction of receptor activator of NF-κB ligand (RANKL, also called TNF-related activation-induced cytokine: TRANCE) in osteoblasts. In cocultures of mouse bone marrow cells and osteoblasts, 1,25(OH)2D3 induced osteoclast formation in a dose-dependent manner, with maximum osteoclast formation observed at concentrations greater than 10−9 M of 1,25(OH)2D3. In the presence of bone morphogenetic protein 2 (BMP-2), the maximum formation of osteoclasts was seen with lower concentrations of 1,25(OH)2D3 (greater than 10−11 M), suggesting that BMP-2 enhances osteoclast formation induced by 1,25(OH)2D3. In addition, the expressions of RANKL mRNA and proteins were induced by 1,25(OH)2D3 in osteoblasts, and further upregulated by BMP-2. In mouse bone marrow cell cultures without 1,25(OH)2D3, BMP-2 did not enhance osteoclast differentiation induced by recombinant RANKL and macrophage colony-stimulating factor (M-CSF), indicating that BMP-2 does not target osteoclast precursors. Furthermore, BMP-2 up-regulated the expression level of vitamin D receptor (VDR) in osteoblasts. These results suggest that BMP-2 regulates mouse osteoclast differentiation via upregulation of RANKL in osteoblasts induced by 1,25(OH)2D3.

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References

  • Asagiri M, Takayanagi H (2007) The molecular understanding of osteoclast differentiation. Bone 40:251–264

    Article  CAS  PubMed  Google Scholar 

  • Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342

    Article  CAS  PubMed  Google Scholar 

  • Katagiri T, Takahashi N (2002) Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis 8:147–159

    Article  CAS  PubMed  Google Scholar 

  • Koide M, Murase Y, Yamato K, Noguchi T, Okahashi N, Nishihara T (1999) Bone morphogenetic protein-2 enhances osteoclast formation mediated by interleukin-1α through upregulation of osteoclast differentiation factor and cyclooxygenase-2. Biochem Biophys Res Commun 259:97–102

    Article  CAS  PubMed  Google Scholar 

  • Komori T (2006) Regulation of osteoblast differentiation by transcription factors. J Cell Biochem 99:1233–1239

    Article  CAS  PubMed  Google Scholar 

  • Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A, Khoo W, Wakeham A, Dunstan CR, Lacey DL, Mak TW, Boyle WJ, Penninger JM (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397:315–323

    Article  CAS  PubMed  Google Scholar 

  • Mizuno A, Amizuka N, Irie K, Murakami A, Fujise N, Kanno T, Sato Y, Nakagawa N, Yasuda H, Mochizuki S, Gomibuchi T, Yano K, Shima N, Washida N, Tsuda E, Morinaga T, Higashio K, Ozawa H (1998) Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem Biophys Res Commun 247:610–615

    Article  CAS  PubMed  Google Scholar 

  • Mizuno A, Kanno T, Hoshi M, Shibata O, Yano K, Fujise N, Kinosaki M, Yamaguchi K, Tsuda E, Murakami A, Yasuda H, Higashio K (2002) Transgenic mice overexpressing soluble osteoclast differentiation factor (sODF) exhibit severe osteoporosis. J Bone Miner Metab 20:337–344

    Article  CAS  PubMed  Google Scholar 

  • Mori K, Kitazawa R, Kondo T, Maeda S, Yamaguchi A, Kitazawa S (2006) Modulation of mouse RANKL gene expression by Runx2 and PKA pathway. J Cell Biochem 98:1629–1644

    Article  CAS  PubMed  Google Scholar 

  • Notoya M, Otsuka E, Yamaguchi A, Hagiwara H (2004) Runx-2 is not essential for the vitamin D-regulated expression of RANKL and osteoprotegerin in osteoblastic cells. Biochem Biophys Res Commun 324:655–660

    Article  CAS  PubMed  Google Scholar 

  • O'Brien CA, Gubrij I, Lin SC, Saylors RL, Manolagas SC (1999) STAT3 activation in stromal/osteoblastic cells is required for induction of the receptor activator of NF-κB ligand and stimulation of osteoclastogenesis by gp130-utilizing cytokines or interleukin-1 but not 1,25-dihydroxyvitamin D3 or parathyroid hormone. J Biol Chem 274:19301–19308

    Article  PubMed  Google Scholar 

  • Otsuka E, Notoya M, Hagiwara H (2003) Treatment of myoblastic C2C12 cells with BMP-2 stimulates vitamin D-induced formation of osteoclasts. Calcif Tissue Int 73:72–77

    Article  CAS  PubMed  Google Scholar 

  • Sato M, Nakamichi Y, Nakamura M, Sato N, Ninomiya T, Muto A, Nakamura H, Ozawa H, Iwasaki Y, Kobayashi E, Shimizu M, DeLuca HF, Takahashi N, Udagawa N (2007) New 19-nor-(20S)-1α, 25-dihydroxyvitamin D3 analogs strongly stimulate osteoclast formation both in vivo and in vitro. Bone 40:293–304

    Article  CAS  PubMed  Google Scholar 

  • Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy 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

    Article  CAS  PubMed  Google Scholar 

  • Suda T, Jimi E, Nakamura I, Takahashi N (1997) Role of 1α, 25-dihydroxyvitamin D3 in osteoclast differentiation and function. Methods Enzymol 282:223–235

    Article  CAS  PubMed  Google Scholar 

  • Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20:345–357

    Article  CAS  PubMed  Google Scholar 

  • Takahashi N, Akatsu T, Udagawa N, Sasaki T, Yamaguchi A, Moseley JM, Martin TJ, Suda T (1988a) Osteoblastic cells are involved in osteoclast formation. Endocrinology 123:2600–2602

    Article  CAS  PubMed  Google Scholar 

  • Takahashi N, Yamana H, Yoshiki S, Roodman GD, Mundy GR, Jones SJ, Boyde A, Suda T (1988b) Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology 122:1373–1382

    Article  CAS  PubMed  Google Scholar 

  • Takahashi N, Akatsu T, Sasaki T, Nicholson GC, Moseley JM, Martin TJ, Suda T (1988c) Induction of calcitonin receptors by 1α, 25-dihydroxyvitamin D3 in osteoclast-like multinucleated cells formed from mouse bone marrow cells. Endocrinology 123:1504–1510

    Article  CAS  PubMed  Google Scholar 

  • Takeda S, Yoshizawa T, Nagai Y, Yamato H, Fukumoto S, Sekine K, Kato S, Matsumoto T, Fujita T (1999) Stimulation of osteoclast formation by 1, 25-dihydroxyvitamin D requires its binding to vitamin D receptor (VDR) in osteoblastic cells: studies using VDR knockout mice. Endocrinology 140:1005–1008

    Article  CAS  PubMed  Google Scholar 

  • Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett FS 3rd, Frankel WN, Lee SY, Choi Y (1997) 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 272:25190–25194

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto N, Akiyama S, Katagiri T, Namiki M, Kurokawa T, Suda T (1997) Smad1 and smad5 act downstream of intracellular signalings of BMP-2 that inhibits myogenic differentiation and induces osteoblast differentiation in C2C12 myoblasts. Biochem Biophys Res Commun 238:574–580

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto Y, Udagawa N, Matsuura S, Nakamichi Y, Horiuchi H, Hosoya A, Nakamura M, Ozawa H, Takaoka K, Penninger JM, Noguchi T, Takahashi N (2006) Osteoblasts provide a suitable microenvironment for the action of receptor activator of nuclear factor-κB ligand. Endocrinology 147:3366–3374

    Article  CAS  PubMed  Google Scholar 

  • Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara Y, Kawakami T, Arioka K, Sato H, Uchiyama Y, Masushige S, Fukamizu A, Matsumoto T, Kato S (1997) Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet 16:391–396

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan

    Keita Tachi, Masamichi Takami, Baohong Zhao, Atsushi Yamada, Yoichi Miyamoto & Ryutaro Kamijo

  2. Department of Prosthodontics, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan

    Keita Tachi & Kazuyoshi Baba

  3. Department of Oral Physiology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan

    Ayako Mochizuki & Tomio Inoue

Authors
  1. Keita Tachi
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  2. Masamichi Takami
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  3. Baohong Zhao
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  4. Ayako Mochizuki
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  5. Atsushi Yamada
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  6. Yoichi Miyamoto
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  7. Tomio Inoue
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  8. Kazuyoshi Baba
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  9. Ryutaro Kamijo
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Correspondence to Masamichi Takami.

Additional information

This work was supported by research grants from the Ministry of Education and Culture of Japan and Naito Foundation.

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Tachi, K., Takami, M., Zhao, B. et al. Bone morphogenetic protein 2 enhances mouse osteoclast differentiation via increased levels of receptor activator of NF-κB ligand expression in osteoblasts. Cell Tissue Res 342, 213–220 (2010). https://doi.org/10.1007/s00441-010-1052-y

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  • DOI: https://doi.org/10.1007/s00441-010-1052-y

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