Alendronate Induces Mineralization in Mouse Osteoblastic MC3T3-E1 Cells: Regulation of Mineralization-Related Genes

Abstract

Alendronate, an aminobisphosphonate, is an effective reagent to reduce fracture risk in osteoporotic patients. Although several studies suggest that bisphosphonates affect osteoblast differentiation, how they affect the genes relating to the mineralization step remains unknown. The present study was performed to clarify the effects of alendronate on mineralization and its related genes in mouse osteoblastic MC3T3-E1 cells. Alendronate at 10 (-8) and 10 (-7) M induced mineralization in MC3T3-E1 cells. As for the genes that suppress mineralization, alendronate enhanced the level of PC-1 mRNA in a dose-dependent manner in 7-day cultures in semiquantitative RT-PCR, although it reduced the levels of PC-1 mRNA in 21-day cultures. On the other hand, alendronate did not affect the levels of ANK, osteopontin and matrix Gla protein mRNA in both 7- and 21-day cultures. Moreover, alendronate reduced the level of osteocalcin mRNA at 10 (-7) and 10 (-6) M in 14-day cultures of these cells. As for the expression of alkaline phosphatase (ALP), an important positive regulator of mineralization in osteoblasts, alendronate enhanced the levels of ALP mRNA and protein at 10 (-7)-10 (-5) M. In conclusion, low-dose alendronate induced mineralization in mouse osteoblastic cells. The regulation of PC-1, osteocalcin and ALP by alendronate might play some role in these effects.

Alendronate–calcium phosphate hybrid films promoted the osteoblast differentiation and inhibited osteoclastogenic activity

“…Proliferation of MG63 cells was decreased when the cells were cultured on calcium phosphate [30][31][32]. We obtained the similar result to these reports when we cultured MG63 cells on CP.…”

Promotion of Bone Formation around Alendronate-immobilized Screw-Type Titanium Implants after Implantation into Rat Molar Tooth Sockets

“…Some researchers reported that alendronate enhanced the osteogenic differentiation of osteoblasts and bone marrow mesenchymal stem cells. 43,44) Moon et al 45) demonstrated that alendronate-immobilized titanium implant surface showed enhancement of osteoblast function as well as h and then decline gradually. McKenzie et al 48) also investigated the elution of zolendronic acid from a porous apatite-coated tantalum implant using a radio-labeling technique and claimed that the elution of zoledronic acids mainly localized in peri-implant bone, and peri-implant bone formation was strongly confined to the immediate space around the implant border.…”

Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats

“…In parallel with our results, Runx2 expression was lower in alendronatetreated Rhesus monkeys with OVX, as compared with cathepsin K inhibitor-treated ones. 41 Since there is histological evidence of new bone formation in melatonin-or alendronate-treated OVX groups, it appears that bone mineralization observed in our study is not solely associated with the expression of the Runx2 gene, but other genes involved in osteoblast differentiation or osteoclast/bone resorption 42 could have more dominant roles in the in vivo regulatory mechanisms of alendronate or melatonin on osteoporotic bone tissue.…”