Differential effects of transforming growth factor-beta on osteoclast-like cell formation in mouse marrow culture: relation to the effect of zinc-chelating dipeptides

Peptides. 1995;16(8):1483-8. doi: 10.1016/0196-9781(95)02030-6.

Abstract

The effect of transforming growth factor-beta (TGF-beta) on osteoclast-like cell formation in mouse marrow culture in vitro was investigated. The bone marrow cells were cultured for 7 days in alpha-minimal essential medium containing a well-known bone resorbing agent. Osteoclast-like cell formation was estimated with staining for tartrate-resistant acid phosphatase (TRACP), a marker enzyme of osteoclasts. The presence of TGF-beta (10(-13)-10(-11) M) caused a significant increase in the number of osteoclast-like multinucleated cells (MNCs); the maximum effect was seen with 10(-12) MTGF-beta. With a higher concentration (10(-10) M) of TGF-beta, the growth factor dramatically inhibited the 1,25-dihydroxyvitamin D5 [1,25(OH)2D3; 10(-8) M]-induced formation of osteoclast-like MNCs. This inhibitory effect was also seen in the formation of osteoclast-like MNCs stimulated by parathyroid hormone (10(-8) M), prostaglandine E2 (10(-6) M), and interleukin-1 alpha (50 U/ml). The stimulatory effect of TGF-beta (10(-12) M) on osteoclast-like MNCs formation was inhibited by zinc sulfate (10(-6) M) or zinc-chelating dipeptide [beta-alanyl-L-histidinato zinc (AHZ), 10(-6) M]. The stimulating effect of TGF-beta was markedly weakened by the presence of EGTA (0.5 mM), a chelator of Ca2+. The inhibitory effect of zinc compounds was not seen in the presence of EGTA. Moreover, the inhibitory effect of TGF-beta (10(-10) M), zinc sulfate (10(-6) M), or AHZ (10(-6) M) on osteoclast-like MNCs formation was not demonstrated in mature osteoclastic cells, although calcitonin (3 x 10(-8) M) significantly inhibited the osteoclastic formation. The present study demonstrates that TGF-beta has a stimulating and an inhibiting effect on osteoclast-like cell formation in mouse marrow culture, and that zinc can inhibit the stimulatory effect of TGF-beta.

MeSH terms

  • Animals
  • Bone Marrow / drug effects*
  • Bone Marrow Cells*
  • Carnosine / analogs & derivatives*
  • Carnosine / pharmacology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Chelating Agents / pharmacology
  • Dipeptides / chemistry
  • Dipeptides / pharmacology*
  • Mice
  • Organometallic Compounds / pharmacology*
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects*
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta / physiology
  • Zinc / pharmacology*
  • Zinc Compounds

Substances

  • Chelating Agents
  • Dipeptides
  • Organometallic Compounds
  • Transforming Growth Factor beta
  • Zinc Compounds
  • polaprezinc
  • Carnosine
  • Zinc