Zoledronate inhibits receptor activator of nuclear factor kappa-B ligand-induced osteoclast differentiation via suppression of expression of nuclear factor of activated T-cell c1 and carbonic anhydrase 2

Nakagawa, Takayuki; Ohta, Kouji; Kubozono, Kazumi; Ishida, Yasushi; Naruse, Takako; Takechi, Masaaki; Kamata, Nobuyuki

doi:10.1016/j.archoralbio.2014.09.012

Cited by 25 publications

(23 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Any imbalance in the communication between OPG, RANK, and RANKL proteins can lead to alterations in the quality of the formed mineralized tissue (Shalhoub et al, 1999;Suda et al, 1999;Manrique et al, 2015). Some studies have demonstrated that BPs inhibit the expression of RANKL, increase levels of OPG, and reduce osteoclast differentiation (Nakagawa et al, 2015;Mackie et al, 2001;Viereck et al, 2002). In contrast, Cardemil et al (2015) observed similar expression of RANKL and OPG in alveolar bone samples from patients with and without ONJ after BP treatment.…”

Section: Introductionmentioning

confidence: 99%

Long-term therapy with intravenous zoledronate increases the number of nonattached osteoclasts

Nagata

Messora

Antoniali

et al. 2017

Journal of Cranio-Maxillofacial Surgery

View full text Add to dashboard Cite

The purpose of this study was to investigate the influence of long-term therapy with intravenous zoledronate (ZA) on the healing of extraction sockets in rats. Forty rats, divided into groups C (Control) and Z (Zoledronate), received intravenous injections of either saline solution or ZA for 24 weeks. Their right maxillary incisor was extracted. Euthanasia was performed at 7 or 28 days postoperative. Histomorphometric (Newly Formed Bone Area) and immunohistochemical (RANKL, OPG and TRAP) analyses were performed. Data were statistically analyzed (ANOVA, Tukey's test and Kruskal-Wallis, Dunn's Multiple Comparison test).Groups C and Z showed similar new bone area, RANKL and OPG immunolabeling. The number of TRAP-positive multinucleated cells was significantly higher in Group Z than in Group C at 28 days. A significantly higher proportion of nonattached osteoclasts were seen in Group Z than in Group C at both periods of analysis. Long-term therapy with intravenous ZA stimulated nonattached osteoclast formation in extraction sockets in rats, thus decreasing local bone resorption. However, it did not influence bone formation by osteoblasts.

show abstract

Section: Introductionmentioning

confidence: 99%

Long-term therapy with intravenous zoledronate increases the number of nonattached osteoclasts

Nagata

Messora

Antoniali

et al. 2017

Journal of Cranio-Maxillofacial Surgery

View full text Add to dashboard Cite

show abstract

“…Currently, there have been only a limited number of investigations into the effects of bisphosphonates on gene expression using cell culture models [8,9,15,16]. Nakagawa et al (2015) carried out a microarray analysis to identify the molecular targets of ZA in the RANKL signaling pathway and factors associated with osteoclastogenesis using osteoclast precursor cells (purchased from the Primary Cell Co., Ltd. Sapporo, Japan) [17]. The results of their microarray analysis identified two genes, nuclear factor of activated T-cell c1 (NFATc1) and carbonic anhydrase 2 (CAII), that were significantly down-regulated in the presence of ZA and restored by GGOH.…”

Section: Discussionmentioning

confidence: 99%

“…The present study focused on the reported antiangiogenic effects of ZA and the potential of GGOH to restore angiogenic gene functioning [6]. The use of primary human osteoclasts differentiated from blood monocytes collected from three participants was in contrast with recent studies that used osteoclasts derived from mice to investigate the effect of ZA [17][18][19]. To the authors' best knowledge, this is the first cell culture study that utilized a primary human osteoclast cell culture model to determine the effects of ZA on angiogenic gene expression.…”

Section: Discussionmentioning

confidence: 99%

Effects of zoledronic acid and geranylgeraniol on angiogenic gene expression in primary human osteoclasts

et al. 2020

View full text Add to dashboard Cite

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication associated with bisphosphonate treatment. Zoledronic acid (ZA) is a commonly used bisphosphonate due to its effectiveness in increasing bone density and reducing skeletal events, with evidence that it alters angiogenesis. Replacement of the mevalonate pathway using geranylgeraniol (GGOH) was studied to determine the effects of ZA on angiogenic gene expression in primary human osteoclasts. Osteoclast cultures were generated from peripheral blood mononuclear cells of three patients using the peripheral blood mononuclear cell isolation. These cells were phenotyped by phase-contrast microscopy, tartrate-resistant acid phosphatase staining, and pit assays. Primary osteoclasts were found to express a number of key angiogenic molecules at very high levels. Gene expression levels for 84 human angiogenic factors were determined using PCR arrays. Three genes with significant fold regulation (FR) in response to ZA were as follows: tumor necrosis factor (FR = +2.57, P = 0.050), CXCL9 (FR = +39.48, P = 0.028), and CXCL10 (FR = +18.52, P = 0.0009). The co-addition of geranylgeraniol with ZA resulted in the significant down-regulation of these three genes along with CCL2, TGFBR1, ENG, and CXCL1. GGOH reversed the gene changes induced by ZA and may offer a promising treatment for BRONJ.

show abstract

“…We reported different hypothetical mechanism of anti-MM activity of zoledronic acid, for which there is actually no consensus, for this reason, according with the results found in solid tumors, we explored the contribution of bisphosphonates in anti-MM activity studying its potential anti-angiogenic effect based on modification of cytokines which are pivotal in this pathogenic mechanism [11][12][13][14][15][16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Cytokines Behavior in Multiple Myeloma Patients during Zoledronic Acid Treatment

Annibali¹,

Petrucci²,

Tirindelli³

et al. 2017

J Blood Lymph

View full text Add to dashboard Cite

Objective: Multiple Myeloma (MM) is characterized by uncoupling of bone resorption from bone formation which leads to the predominance of resorption. Bisphosphonates are chemical compounds that selectively concentrate at the interface of the active osteoclasts and the bone resorption surface where they inhibit osteoclast activity. Aim of this study was to describe cytokines behaviour in MM and to evaluate whether zoledronic acid could have an in vivo anti-angiogenic property in MM as observed in solid tumours.Methods: Serum samples from 29 (16 males and 13 females) consecutive MM patients with lytic bone lesions treated with 4 mg of zoledronic acid were tested for platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumor necrosis factor (TNF α) and insulin growth factor (IGF-I). Basal cytokine levels were compared with the values observed after 1, 2, 7 and 21 days of treatment, using the Wilcoxon's test for nonparametric-dependent continuous variables.Results: A significant increase in IL-6 and TNF α was observed on days 1 and 2. As for VEGF, the levels of this cytokine did not change significantly from basal values during the entire period of observation except for a significant increase day 7 (P=0.0005). Moreover, PDGF significantly decreased (P=0.005) after 2 days from zoledronic acid infusion. Conclusions:From this study appears that in MM, treatment with zoledronic acid induces a transient reduction in PDGF according with previous studies in solid cancer, while the increase of IL-6 and VEGF could be related through a paracrine mechanism. The anti-myeloma effect of this drug could be driven through this mechanism.

show abstract

Zoledronate inhibits receptor activator of nuclear factor kappa-B ligand-induced osteoclast differentiation via suppression of expression of nuclear factor of activated T-cell c1 and carbonic anhydrase 2

Cited by 25 publications

References 34 publications

Long-term therapy with intravenous zoledronate increases the number of nonattached osteoclasts

Long-term therapy with intravenous zoledronate increases the number of nonattached osteoclasts

Effects of zoledronic acid and geranylgeraniol on angiogenic gene expression in primary human osteoclasts

Cytokines Behavior in Multiple Myeloma Patients during Zoledronic Acid Treatment

Contact Info

Product

Resources

About