The effects of bisphosphonates on osteoblasts in vitro

Naidu, Aparna; Dechow, Paul C.; Spears, Robert; Wright, John M.; Kessler, Harvey P.; Opperman, Lynne A.

doi:10.1016/j.tripleo.2008.03.036

Cited by 63 publications

(32 citation statements)

References 55 publications

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“…Naidu et al [44] reported that TGF-β1 expression was increased by BPs, and others have found that this growth factor enhances proliferation and osteoblast differentiation in its initial phase but inhibits its differentiation and maturation and suppresses matrix mineralization in later phases [45,46]. In the present study, the three BPs increased osteoblast proliferation and reduced ALP synthesis and mineralization nodule formation in inverse relation to their dose, which may be explained by the BP-induced increase in TGF-β1 synthesis, which would in turn be consistent with the reduced expression of co-stimulatory molecules in the presence of this growth factor.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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“…Previous studies showed the effects of ZA treatment on different cell types, including osteoblasts [6,32]. However, these studies evaluated ZA treatment for short periods, considering the IV infusion contact period (IV distribution).…”

Section: Discussionmentioning

confidence: 99%

“…Evaluating the therapeutic and over-therapeutic doses of bisphosphonates on osteoblasts, Naidu et al [32] demonstrated that these kinds of drugs are capable of reducing viability and protein expression by osteoblasts in culture. In addition, Orris et al [21] reported that osteoblasts exposed for 14 days to ZA at 10 and 100 n M , and 1 and 10 μ M decreased the numbers of viable cells by 20, 30, 40 and 90%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Zoledronic Acid Inhibits Human Osteoblast Activities

et al. 2013

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Background: Bisphosphonates are potent inhibitors of bone resorption. These kinds of drugs, which are used for the treatment of osteolytic diseases, have been associated with the occurrence of oral osteonecrosis, especially in patients over 60 years old. Current studies have demonstrated that the cytotoxic effects of bisphosphonates on osteoblasts play an important role in oral osteonecrosis development. Objective: The aim of this study was to evaluate the effect of long-term application of a highly potent bisphosphonate - zoledronic acid (ZA) - on human osteoblasts in vitro. Methods: Human osteoblasts (MG63 cell line) were seeded for 72 h in wells of 24-well plates. The Dulbecco's modified Eagle's medium (DMEM) was then replaced by culture medium without fetal bovine serum (FBS), and the cells were incubated for an additional 24 h, after which ZA was added to the DMEM without FBS and incubated in contact with osteoblasts for 7, 14 or 21 days. Cell viability (CV), total protein production (TPP), alkaline phosphatase (ALP) activity, mineral nodule formation (MNF), and gene expression of ALP and osteocalcin (OCN), as well as cell morphology by scanning electronic microscopy, were evaluated. Data were statistically analyzed by Kruskal-Wallis and Mann-Whitney tests, with a significance level of 5%. Results: The cytotoxic effects of ZA on osteoblasts were characterized by reduction of CV, TPP, ALP and MNF production. In addition, ZA MNF caused a decrease in gene expression of ALP and OCN, as well as intense cell morphology alterations. All these negative effects of ZA were concentration and period dependent. Conclusion: Both concentrations of ZA (1 and 5 μM) caused cytotoxic effects to osteoblasts which reduced the production and expression of proteins that play an important role in bone matrix synthesis and mineralization.

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“…Several hormones and cytokines regulate the production of RANKL and OPG by osteoblasts, including parathyroid hormone (PTH), PTH-related protein (PTH-rP), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3 or vitamin D], estrogens, transforming growth factor (TGF), interleukin-1 (IL-1), and tumor-necrosis factor (TNF) (reviewed in [19]). Several studies have analyzed the effects of alendronate and other BPs in OB (stromal cells, primary cells and OB cell lines) and have shown that these drugs influence the differentiation, proliferation and maturation [9,[20][21][22][23][24][25][26][27][28], apoptosis [9,20,[29][30][31][32][33] and gene expression [13-16, 24, 26, 30, 34, 35] of these cells. Despite this, the knowledge of the effect of alendronate on the mature osteoblast cells, especially in the OPG/RANKL system, is still incomplete and it has not been totally clarified.…”

Section: Introductionmentioning

confidence: 99%

The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts

Enjuanes

Ruiz-Gaspà²,

Peris³

et al. 2010

Endocr

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Alendronate is a well-established treatment for osteoporosis and suppresses bone resorption by a direct effect on osteoclasts and their precursors. The effect of alendronate on osteoclasts is produced, at least in part, by the receptor activator of nuclear factor kappaB ligand (RANKL) and the osteoprotegerin (OPG) synthesized by the osteoblasts. This study analyzes the effect of alendronate in cell viability, alkaline phosphatase (ALP) activity and RANKL and OPG expression in primary human osteoblasts (hOB). Alendronate at concentrations lower than 10⁻⁵ M did not have a toxic effect on hOB in vitro and did not modify the ALP activity at least for 72 h. Alendronate did not change OPG expression in basal, 10% fetal bovine serum (FBS), and vitamin D-treated cultures. Similar results were observed at the protein level. Unexpectedly, alendronate at 10⁻⁷ and 10⁻⁵ M concentrations increased the RANKL expression with the presence of vitamin D in differentiated hOB, and this induction of RANKL mRNA levels by alendronate was dose-dependent. However, this effect was not observed in basal and 10% FBS culture conditions. Thus, we conclude that alendronate does not affect the ALP activity and OPG gene expression in differentiated hOB, but may increase RANKL gene expression induced by vitamin D.

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The effects of bisphosphonates on osteoblasts in vitro

Cited by 63 publications

References 55 publications

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

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

Zoledronic Acid Inhibits Human Osteoblast Activities

The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts

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