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. Design and 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 24 h 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(-3) mol/l) but not 10(-8) mol/l hPTH(3-34) downregulated 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.