Prostaglandin E2 stimulates osteoclast-like cell formation and bone-resorbing activity via osteoblasts: role of cAMP-dependent protein kinase

J Bone Miner Res. 1996 Jan;11(1):62-71. doi: 10.1002/jbmr.5650110110.

Abstract

Prostaglandin E2 (PGE2) is an important local regulator in bone. The present study was performed to investigate the effect of PGE2 on osteoclast-like cell formation and bone-resorbing activity of mature osteoclasts in the presence or absence of osteoblasts, PGE2 (10(-8) to 10(-6) M) significantly stimulated osteoclast-like cell formation in osteoblast-containing mouse bone cell cultures, although it did not affect osteoclast-like cell formation from hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor in osteoblast-free mouse spleen cell cultures. The conditioned medium from osteoblastic UMR-106 cells pretreated with PGE2 (10(-8) and 10(-6) M) significantly stimulated osteoclast-like cell formation from hemopoietic blast cells. PGE2 also significantly stimulated the bone-resorbing activity of mature osteoclasts in osteoblast-containing mouse bone cell cultures. In contrast, PGE2 significantly inhibited the bone-resorbing activity and osteopontin mRNA expression in isolated rabbit osteoclasts. Rp-cAMPS, a direct protein kinase (PKA) antagonist, significantly inhibited PGE2-stimulated osteoclast-like cell formation and the bone-resorbing activity of mature osteoclasts, although protein kinase C inhibitors, dantrolene (an inhibitor of calcium release from the intracellular calcium pool) and voltage-dependent calcium channel blockers did not affect PGE2-stimulated osteoclast-like cell formation. In conclusion, PGE2 stimulated osteoclast-like cell formation and bone-resorbing activity in mouse bone cell cultures presumably through osteoblasts. The activation of PKA is linked to PGE2-stimulated osteoclast-like cell formation and bone-resorbing activity.

MeSH terms

  • Animals
  • Bone Resorption / chemically induced*
  • Bone Resorption / enzymology*
  • Bone Resorption / pathology
  • Calcium / metabolism
  • Cell Communication
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Culture Media, Conditioned
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Dinoprostone / pharmacology*
  • Enzyme Activation / drug effects
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Insulin-Like Growth Factor I / antagonists & inhibitors
  • Insulin-Like Growth Factor I / physiology
  • Mice
  • Mice, Inbred ICR
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / enzymology*
  • Osteoclasts / cytology
  • Osteoclasts / drug effects*
  • Osteoclasts / enzymology*
  • Osteopontin
  • Prostaglandins / physiology
  • Protein Kinase C / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sialoglycoproteins / genetics
  • Signal Transduction

Substances

  • Culture Media, Conditioned
  • Prostaglandins
  • RNA, Messenger
  • Sialoglycoproteins
  • Spp1 protein, mouse
  • Osteopontin
  • Insulin-Like Growth Factor I
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Dinoprostone
  • Calcium