Effects of transforming growth factor-β1 on formation and activation of osteoclasts

Hiroshi Kamioka, Keishi Ishikawa, Kayo Tanaka, Takuya Sato, Ken Ichi Tezuka, Kenji Hiura, Koji Sumitani, Yoshiyuki Hakeda, Terushige Kawata, Masayoshi Kumegawa

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Transforming growth factor-β1 (TGF-β1) has biological functions in various types of cells. However, its roles in the regulation of osteoclast formation and function are unclear. To examine them, we employed a culture system in which unfractionated cells obtained from long bones of 13-day-old mice were cultured on a dentine slice. We found that TGF-β1 has a potent inhibitory effect on osteoclastic bone resorption at a dose of 0.2-5 ng/ml. By electron microscopy the osteoclasts appeared to have fewer mitochondria and ruffled borders than those in control cultures. But in the presence of 1,25-dihydroxyvitamin D3, [1,25-(OH)2D3], TGF-β1 at a dose of 0.2-1 ng/ml stimulated the formation of osteoclasts from unfractionated bone cell cultures in which preexistent osteoclasts had degenerated. Thus, using stromal cell-free he-mopoietic blast cells, we examined the direct action of TGF-β1 on osteoclast precursors. Although TGF-β1 inhibited tartrate-resistant acid phosphatase-positive (TRAP) multinucleate cell (MNC) formation induced by 1,25-(OH)2D3, the conditioned medium (CM) of TGF-β1-treated MC3T3-E1 cells stimulated such formation. These results suggest that TGF-β1 inhibits osteoclastic bone resorption but stimulates osteoclast formation via the action of factor(s) produced by TGF-β1-treated osteoblasts in the presence of 1,25-(OH)2D3.

Original languageEnglish
Pages (from-to)3-9
Number of pages7
JournalJournal of Bone and Mineral Metabolism
Issue number1
Publication statusPublished - Mar 1 1995
Externally publishedYes


  • TGF-β
  • bone resorption
  • osteoclast

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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    Kamioka, H., Ishikawa, K., Tanaka, K., Sato, T., Tezuka, K. I., Hiura, K., Sumitani, K., Hakeda, Y., Kawata, T., & Kumegawa, M. (1995). Effects of transforming growth factor-β1 on formation and activation of osteoclasts. Journal of Bone and Mineral Metabolism, 13(1), 3-9. https://doi.org/10.1007/BF01771798