Inhibitory effect of zinc-chelating dipeptide on parathyroid hormone-stimulated osteoclast-like cell formation in mouse marrow cultures: involvement of calcium signaling

Peptides. 1995;16(4):629-33. doi: 10.1016/0196-9781(95)00014-b.


A possible mechanism of zinc action inhibiting the PTH-induced osteoclast-like cell formation in mouse marrow culture system in vitro was investigated. Bone marrow cells were cultured for 7 days in alpha-minimal essential medium containing a well-known bone-resorbing agent parathyroid hormone (1-34) (PTH). Osteoclast-like cell formation was estimated with staining for tartrate-resistant acid phosphatase (TRACP), a marker enzyme of osteoclasts. The effect of zinc sulfate (10(-6) M) or beta-alanyl-L-histidinato zinc (AHZ; 10(-6) M) inhibiting the PTH (10(-8) M)-induced osteoclast-like cell formation was clearly seen in the absence or presence of theophylline (10(-4) M). However, zinc compounds did not inhibit the stimulatory effect of dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP; 10(-4) M) on osteoclast-like cell formation. The stimulating effect of PTH (10(-8) M) on osteoclast-like cell formation was clearly weakened (about 50%) in the presence of EGTA (1.0 mM) or dibucaine (10(-5) M). Phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator (10(-8) to 10(-6) M), clearly stimulated osteoclast-like cell formation. PMA effect was inhibited by the presence of AHZ (10(-6) M) or zinc sulfate (10(-8) M). However, the inhibitory effect of zinc compounds was not seen in the presence of both PTH (10(-8) M) and PMA (10(-6) M). The present findings suggest that zinc compounds inhibit PTH-stimulated osteoclast-like cell formation mediated through the Ca(2+)-dependent activation of protein kinase C.

MeSH terms

  • Animals
  • Bone Marrow / drug effects*
  • Bone Marrow Cells
  • Calcium / physiology*
  • Carnosine / analogs & derivatives
  • Carnosine / pharmacology
  • Cell Division / drug effects
  • Cells, Cultured
  • Chelating Agents / pharmacology*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Organometallic Compounds / pharmacology
  • Osteoclasts / drug effects*
  • Parathyroid Hormone / antagonists & inhibitors*
  • Signal Transduction / drug effects
  • Stimulation, Chemical
  • Sulfates / pharmacology
  • Zinc Compounds / pharmacology
  • Zinc Sulfate
  • Zinc*


  • Chelating Agents
  • Organometallic Compounds
  • Parathyroid Hormone
  • Sulfates
  • Zinc Compounds
  • polaprezinc
  • Zinc Sulfate
  • Carnosine
  • Zinc
  • Calcium