Involvement of osteoprotegerin/osteoclastogenesis inhibitory factor in the stimulation of osteoclast formation by parathyroid hormone in mouse bone cells.
OBJECTIVE
Recently, osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) has been shown to inhibit osteoclast differentiation. On the other hand, we have reported that parathyroid hormone (PTH) stimulated osteoclast formation, presumably through a PTH-responsive cAMP-dependent protein kinase (PKA) pathway, in mouse bone cells.


METHODS
The present study was performed to examine how OPG/OCIF expression is regulated by PTH and to further investigate the possible involvement of OPG/OCIF in the stimulation of osteoclast formation by PTH in mouse bone cells. OPG/OCIF mRNA expression was analyzed by Northern hybridization after 24h treatments of mouse whole bone cells and mouse stromal cell line, ST2 cells with PTH or various second messenger analogs.


RESULTS
Human (h) PTH(1-34) (10(-10) and 10(-8)mol/l) but not 10(-8)mol/l hPTH(3-34) down-regulated OPG/OCIF mRNA expression in mouse bone cells. Dibutyryl cAMP, but not phorbol ester, an activator of protein kinase C, or A23187, a calcium ionophore, down-regulated it. The same was also observed in ST2 cells, suggesting that stromal cells are responsible for the inhibitory effect of PTH and cAMP analogs on OPG/OCIF mRNA expression in mouse bone cells.


CONCLUSIONS
The present study indicates that PTH down-regulates OPG/OCIF mRNA expression through the PKA pathway in stromal cells, which would result in the stimulation of osteoclast formation.
Kanzawa
M
M
Third Division, Department of Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Sugimoto
T
T
Kanatani
M
M
Chihara
K
K
D000818:Animals; D001842:Bone and Bones / Q000166:cytology* / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000166:cytology*; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D017154:Stromal Cells / Q000166:cytology
D006023:Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse