Exp Mol Med.  2002 May;34(2):145-151.

Inhibitory action of bisphosphonates on bone resorption does not involve the regulation of RANKL and OPG expression

• Kim YH
• Kim GS
• Baek JH

Abstract

The mechanism of inhibitory action of bisphosphonates on bone resorption is not fully elucidated. Osteoclast formation and activity are regulated by osteoblast-derived factors such as the osteoclast differentiating factor, receptor activator of NF-kappaB ligand (RANKL) and the inhibitor, osteoprotegerin (OPG). To investigate in vitro effects of bisphosphonates on mouse osteoblastic cells, we examined the expression levels of RANKL and OPG in the cells treated with alendronate or pamidronate (10(-8) approximately 10(-5)M) alone, or combined with 10 nM of 1,25-(OH)2VitD3 for 24 or 48 h. Various concentrations of alendronate and pamidronate did not change the mRNA expression of RANKL and OPG consistently irrespective of 1,25-(OH)2VitD3 presence. When added into cocultures of mouse osteoblastic cells and bone marrow cells, both alendronate and pamidronate inhibited osteoclast formation and bone resorption but failed to alter the RANKL and OPG mRNA expression. These results indicate that the inhibition of bone resorption by bisphosphonates is not mediated by the regulation of RANKL and OPG expression.

MeSH Terms

Alendronate/metabolism
Animals
*Bone Resorption/drug therapy
Carrier Proteins/*genetics
Cells, Cultured
Diphosphonates/metabolism/*pharmacology
Gene Expression Regulation/*drug effects
Glycoproteins/*genetics
Membrane Glycoproteins/*genetics
Mice
Mice, Inbred ICR
Osteoblasts/drug effects
Osteoclasts/drug effects
Receptors, Cytoplasmic and Nuclear/*genetics
Reverse Transcriptase Polymerase Chain Reaction