Regulation of Osteoclasts via Osteoblasts by Alendronate

Kim, Hyunjin; Kim, Min Seok; Kim, Tae Sung; Lee, Eun Joo; Park, Ha Ok; Kim, Baik Yoon; Kim, Sunhun

Abstract

Bisphosphonates have been used for the prevention of pathological bone resorption and its related disease for their high affinity to hydroxyapatite and direct effects on osteoclasts. Several studies have shown that in vitro the potency of bisphosphonates for osteoclasts is not coincident with in vivo results, which proposes other mechanisms may be involved in their inhibition of bone resorption. Osteoblasts have paracrine regulation for osteoclast activities and formation. Thus, it is hypothesized that bisphosphonates may have indirect effects on osteoblasts to regulate osteoclastic bone resorption. This study was carried out to investigate molecular mechanism that alendronate, a nitrogen containing bisphosphponate, acts on osteoblasts to regulate osteoclastic bone resorption in vivo and in vitro system. In vitro MTS system using MC3T3-E1 osteoblastic cell line, absorbance values increased at 10(-10) to 10(-4) M concentration after a day treatment of alendronate. The values decreased at 3 and 5 days after treatment at 10(-5) M higher concentration. Gene expression levels of ALP, OPG and type I collagen were not changed at both 10(-5) M and 10(-6) M. However, MCP-1 and M-CSF notably decreased in their gene expression by the treatment. In vivo system using the rat pup tibia, M-CSF gene expression decreased a lot by alendronate treatment. The number of osteoclasts significantly decreased from trabeculae of femur and tibia in alendronate treated group (p < 0.01). Furthermore, trabeculae themselves underneath the epiphyseal plate were longer in the alendronate treated group (p< 0.01). These results suggested that bisphosphonates can indirectly inhibit osteoclastic bone resorption by affecting osteoblasts to regulate osteoclasts at molecular level.