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

Young Hee Kim,Gwan-Shik Kim,Jeong-Hwa Baek

doi:10.1038/emm.2002.21

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.

Highlights

Bisphosphonates, stable analogs of pyrophosphate, are potent inhibitors of bone resorption and have been used as effective therapeutic agents for the management of osteoporosis and other bone diseases such as Paget's disease (Papapoulos, 1996; Rodan and Fleisch, 1996; Fleisch, 1997)
To investigate whether alendronate and pamidronate affect the mRNA expression of receptor activator of NF-kappaB ligand (RANKL) and OPG in osteoblasts, we performed semiquantitative RT-PCR by using total RNA from mouse osteoblastic cells treated with various concentrations of alendronate or pamidronate
Since the basal level of RANKL mRNA expression in primary osteoblastic cells was too low to be detected by northern blot analysis, we employed RT-PCR analysis instead

Summary

Introduction

Bisphosphonates, stable analogs of pyrophosphate, are potent inhibitors of bone resorption and have been used as effective therapeutic agents for the management of osteoporosis and other bone diseases such as Paget's disease (Papapoulos, 1996; Rodan and Fleisch, 1996; Fleisch, 1997). Inhibition of bone resorption by bisphosphonates has been principally attributed to their inhibitory effect on osteoclasts. They have shown that bisphosphonates promote the release of factors from osteoblasts that inhibit the osteoclast formation and activity.

Results

Conclusion