title: Prostaglandin E2 stimulates osteoclast-like cell formation and bone-resorbing activity via osteoblasts: role of cAMP-dependent protein kinase.
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.
authors.affiliation: Department of Medicine, Kobe University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kaji
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: M
authors.initials: M
authors.lastname: Kanatani
authors.forename: M
authors.initials: M
authors.lastname: Fukase
authors.forename: M
authors.initials: M
authors.lastname: Kumegawa
authors.forename: K
authors.initials: K
authors.lastname: Chihara
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced* / Q000201:enzymology* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D053495:Osteopontin; D011453:Prostaglandins / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics; D015398:Signal Transduction
chemical_list: D017077:Culture Media, Conditioned; D011453:Prostaglandins; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D007334:Insulin-Like Growth Factor I; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D015232:Dinoprostone; D002118:Calcium