Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts

H. Kaneko, T. Arakawa, H. Mano, T. Kaneda, A. Ogasawara, M. Nakagawa, Y. Toyama, Y. Yabe, M. Kumegawa, Y. Hakeda

Research output: Contribution to journalArticle

229 Citations (Scopus)

Abstract

Bone morphogenetic proteins (BMPs) play an important role in various kinds of pattern formation and organogenesis during vertebrate development. In the skeleton, BMPs induce the differentiation of cells of chondrocytic and osteoblastic cell lineage and enhance their function. However, the action of BMPs on osteoclastic bone resorption, a process essential for pathophysiological bone development and regeneration, is still controversial. In this study, we examine the direct effect of BMPs on osteoclastic bone-resorbing activity in a culture of highly purified rabbit mature osteoclasts. BMP-2 caused a dose- and time-dependent increase in bone resorption pits excavated by the isolated osteoclasts. BMP-4 also stimulated osteoclastic bone resorption. The increase in osteoclastic bone resorption induced by BMP-2 was abolished by the simultaneous addition of follistatin, a BMP/activin binding protein that negates their biological activity. Just as it increased bone resorption, BMP-2 also elevated the messenger RNA expressions of cathepsin K and carbonic anhydrase II, which are key enzymes for the degradation of organic and inorganic bone matrices, respectively. Type IA and II BMP receptors (BMPRs), and their downstream signal transduction molecules, Smad1 and Smad5, were expressed in isolated osteoclasts as well as in osteoblastic cells, whereas type IB BMPR was undetectable. BMPs directly stimulate mature osteoclast function probably mediated by BMPR-IA and BMPR-II and their downstream molecules expressed in osteoclasts. The results presented here expand our understanding of the multifunctional roles of BMPs in bone development. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)479-486
Number of pages8
JournalBone
Volume27
Issue number4
DOIs
Publication statusPublished - 2000

Fingerprint

Bone Morphogenetic Protein Receptors
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Osteoclasts
Bone Resorption
Bone and Bones
Type I Bone Morphogenetic Protein Receptors
Follistatin
Bone Development
Type II Bone Morphogenetic Protein Receptors
Cathepsin K
Bone Morphogenetic Protein 4
Carbonic Anhydrase II
Bone Matrix
Bone Regeneration
Organogenesis
Cell Lineage
Protein Binding
Skeleton
Vertebrates

Keywords

  • BMP receptors
  • Bone morphogenetic protein-2 (BMP-2)
  • Bone resorption
  • Osteoclast
  • Smads

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts. / Kaneko, H.; Arakawa, T.; Mano, H.; Kaneda, T.; Ogasawara, A.; Nakagawa, M.; Toyama, Y.; Yabe, Y.; Kumegawa, M.; Hakeda, Y.

In: Bone, Vol. 27, No. 4, 2000, p. 479-486.

Research output: Contribution to journalArticle

Kaneko, H, Arakawa, T, Mano, H, Kaneda, T, Ogasawara, A, Nakagawa, M, Toyama, Y, Yabe, Y, Kumegawa, M & Hakeda, Y 2000, 'Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts', Bone, vol. 27, no. 4, pp. 479-486. https://doi.org/10.1016/S8756-3282(00)00358-6
Kaneko, H. ; Arakawa, T. ; Mano, H. ; Kaneda, T. ; Ogasawara, A. ; Nakagawa, M. ; Toyama, Y. ; Yabe, Y. ; Kumegawa, M. ; Hakeda, Y. / Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts. In: Bone. 2000 ; Vol. 27, No. 4. pp. 479-486.
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AU - Mano, H.

AU - Kaneda, T.

AU - Ogasawara, A.

AU - Nakagawa, M.

AU - Toyama, Y.

AU - Yabe, Y.

AU - Kumegawa, M.

AU - Hakeda, Y.

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