Recombinant human transforming growth factor-alpha stimulates the formation of osteoclast-like cells in long-term human marrow cultures

Transforming growth factor-alpha (TGF-alpha) is synthesized by a variety of tumor cell lines and stimulates osteoclastic bone resorption in vitro. The mechanism by which TGF-alpha increases osteoclast activity is unknown. We used a human marrow culture system that forms osteoclast-like multinucleate...

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Bibliographic Details
Published in:The Journal of clinical investigation 1986-10, Vol.78 (4), p.894-898
Main Authors: TAKAHASHI, N, MACDONALD, B. R, HON, J, WINKLER, M. E, DERYNCK, R, MUNDY, G. R, ROODMAN, G. D
Format: Article
Language:English
Subjects:
Biological and medical sciences
Bone Marrow - drug effects
Bone Marrow Cells
Calcitriol - pharmacology
Cell physiology
Cells, Cultured
Colony-Forming Units Assay
Dose-Response Relationship, Drug
Epidermal Growth Factor - pharmacology
Fundamental and applied biological sciences. Psychology
Humans
Molecular and cellular biology
Osteoclasts - drug effects
Peptides - pharmacology
Recombinant Proteins - pharmacology
Responses to growth factors, tumor promotors, other factors
Time Factors
Transforming Growth Factors
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Summary:Transforming growth factor-alpha (TGF-alpha) is synthesized by a variety of tumor cell lines and stimulates osteoclastic bone resorption in vitro. The mechanism by which TGF-alpha increases osteoclast activity is unknown. We used a human marrow culture system that forms osteoclast-like multinucleated cells (MNCs) to determine the effects of recombinant human TGF-alpha on MNC formation. Addition of 0.01 ng/ml TGF-alpha for the 1st week followed by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] for the subsequent 2 wk significantly increased MNCs. Treatment of these cultures with TGF-alpha without later addition of 1,25(OH)2D3 did not increase MNC formation. Autoradiographic studies revealed that TGF-alpha stimulated proliferation of precursors for MNCs, and 1,25(OH)2D3 increased their rate of fusion into MNCs. Addition of murine epidermal growth factor (EGF) (0.1 ng/ml) followed by 1,25(OH)2D3 also significantly stimulated MNC formation. These data suggest that TGF-alpha and EGF may stimulate bone resorption by increasing the proliferation of osteoclast precursors, which leads to increased numbers of osteoclasts.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI112677