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

J Clin Invest. 1986 Oct;78(4):894-8. doi: 10.1172/JCI112677.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bone Marrow / drug effects
  • Bone Marrow Cells*
  • Calcitriol / pharmacology
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Dose-Response Relationship, Drug
  • Epidermal Growth Factor / pharmacology
  • Humans
  • Osteoclasts / drug effects*
  • Peptides / pharmacology*
  • Recombinant Proteins / pharmacology*
  • Time Factors
  • Transforming Growth Factors


  • Peptides
  • Recombinant Proteins
  • Epidermal Growth Factor
  • Transforming Growth Factors
  • Calcitriol