Effects of Alendronate on the Proliferation and Osteogenic Differentiation of MG-63 Cells

Abstract

Previous studies of the direct actions of bisphosphonates on bone have mainly been limited to their effects on bone-resorbing osteoclasts and little is known about the direct effects of bisphosphonates on osteoblasts. Here we report the direct effects of alendronate on the proliferation and osteogenic differentiation of the MG-63 osteoblast-like cell line. Cell proliferation was determined with the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, osteogenic differentiation was evaluated with an alkaline phosphatase bioassay and by analysis of gene expression by reverse transcription-polymerase chain reaction, and the extent of calcium deposition was measured using Alizarin Red S staining. Alendronate significantly increased cell numbers over control values, with the greatest effect at 10(-8) M. Alkaline phosphatase activity and gene expression of bone morphogenetic protein 2, type I collagen and osteocalcin were increased after alendronate treatment. Alendronate also stimulated calcium deposition. We conclude that alendronate, apart from inhibiting osteoclastic bone resorption, is also a promoter of osteoblast proliferation and maturation.

Nitrogen-containing bisphosphonates modulate the antigenic profile and inhibit the maturation and biomineralization potential of osteoblast-like cells

“…These results are consistent with previous in vitro findings that BPs exert a pro-osteoblastogenic effect at lower concentrations (10 −5 to 10 −9 M) but an inhibitory effect at higher concentrations [34][35][36][37]. In common with previous reports, the present results suggest that BPs exert a beneficial effect on the osteoblast by enhancing its proliferative capacity, although account should be taken of the inverse dose-rate effect observed at the assayed doses.…”

“…The effects of BPs on this differentiation and maturation process are controversial, with some studies finding that BPs reduce ALP synthesis [38] and others suggesting that low doses of nitrogen-containing BPs increase ALP activity and nodule formation. In the present study, low doses of BPs reduced ALP activity and nodule formation [34,35,39], indicating an inhibitory effect on the differentiation and maturation of the osteoblast as bone-forming cell.…”

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

“…CPAH, in particular, appeared to induce greater proliferation than CP and CPAL during 3 and 5 d. This result elucidates that ALN incorporated at the concentration of 10 À4 M was effective for the promotion of MG63 cell proliferation. Previous studies reported that ALN can induce OB proliferation [14,24]. The current study confirmed that its biological activity was effectively maintained even after ALN was incorporated in CP [14,24].…”

“…Previous studies reported that ALN can induce OB proliferation [14,24]. The current study confirmed that its biological activity was effectively maintained even after ALN was incorporated in CP [14,24]. The morphological images of the adherent MG63 cells were taken after culturing 7 d on sample films and shown in Fig.…”

Osteoinductivity of Demineralized Bone Matrix Is Independent of Donor Bisphosphonate Use

“…The chemical properties of these compounds cause them to be retained in the mineral phase of the bone, but whether this affects the organic composition is not known. Bisphosphonates do affect the biosynthetic characteristics of osteoblasts 21,22 , suggesting that there may be alterations in the extracellular matrix as a consequence of use. Recently, it has been found that the addition of bisphosphonates to implanted allograft bone affects the rate of allograft resorption and can affect the success of implants used with allograft 23,24 .…”