Zoledronic acid, an aminobisphosphonate, modulates differentiation and maturation of human dendritic cells

Chen, Yu-Jen; Chao, K.S. Clifford; Yang, Yuh‐Cheng; Hsu, Ming-Ling; Lin, Chin–Ping; Chen, Yu Yawn

doi:10.1080/08923970902814103

Cited by 19 publications

(20 citation statements)

References 35 publications

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“…As we found that ZA inhibits myeloid differentiation in vitro , it can be assumed that the significant increase in the MO-MDSC population found in ZA-treated mice compared with untreated mice are caused by similar inhibitory effects on myeloid differentiation. Inhibition of myeloid differentiation by ZA has also been reported by others (Wolf et al , 2006; Melani et al , 2007; Chen et al , 2009). …”

Section: Discussionsupporting

confidence: 75%

Zoledronic acid impairs myeloid differentiation to tumour-associated macrophages in mesothelioma

et al. 2010

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Background:Suppressive immune cells present in tumour microenvironments are known to augment tumour growth and hamper efficacy of antitumour therapies. The amino-bisphosphonate Zoledronic acid (ZA) is considered as an antitumour agent, as recent studies showed that ZA prolongs disease-free survival in cancer patients. The exact mechanism is a topic of debate; it has been suggested that ZA targets tumour-associated macrophages (TAMs).Methods:We investigate the role of ZA on the myeloid differentiation to TAMs in murine mesothelioma in vivo and in vitro. Mice were intraperitoneally inoculated with a lethal dose of mesothelioma tumour cells and treated with ZA to determine the effects on myeloid differentiation and survival.Results:We show that ZA impaired myeloid differentiation. Inhibition of myeloid differentiation led to a reduction in TAMs, but the number of immature myeloid cells with myeloid-derived suppressor cell (MDSC) characteristics was increased. In addition, ZA affects the phenotype of macrophages leading to reduced level of TAM-associated cytokines in the tumour microenvironment. No improvement of survival was observed.Conclusion:We conclude that ZA leads to a reduction in macrophages and impairs polarisation towards an M2 phenotype, but this was associated with an increase in the number of immature myeloid cells, which might diminish the effects of ZA on survival.

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Section: Discussionsupporting

confidence: 75%

Zoledronic acid impairs myeloid differentiation to tumour-associated macrophages in mesothelioma

et al. 2010

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“…The findings from the present study showed that ZA treatment can suppress Treg levels in peripheral blood while increasing the levels of gdT cells and IL-17 in peripheral blood. BPs can increase the level of IL-17 and gdT cells and decrease the level of Tregs, suggesting that BPs can affect the function of cells in both the innate and acquired immunity pathways [15]. Macrophages could phagocytose apoptotic cells and secrete TGF-b, which could induce Treg differentiation.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine

Mao

et al. 2013

Stem Cells and Development

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Bisphosphonates (BPs), which are used to treat a variety of clinical disorders, have the side effect of jawbone necrosis. Currently, there is no reliable treatment for BP-related osteonecrosis of the jaw (BRONJ) due to a lack of understanding of its pathogenesis. To investigate the pathogenesis of BRONJ and observe the treatment effect of bone marrow mesenchymal stem cell (BMMSC) transplantation, we established a preclinical animal model of BRONJ in miniature pigs (minipigs). After treatment with zoledronic acid, the clinical and radiographic manifestations of BRONJ could be observed in minipigs after first premolar extraction. The biological and immunological properties of BMMSCs were impaired in the BP-treated minipigs. Moreover, the ratio of Foxp3-positive regulatory T-cells (Tregs) in peripheral blood decreased, and interleukin (IL)-17 increased in the serum of BPtreated minipigs. After allogeneic BMMSC transplantation via intravenous infusion, mucosal healing and bone reconstruction were observed; IL-17 levels were reduced; and Tregs were elevated. In summary, we established a clinically relevant BRONJ model in minipigs and tested a promising allogeneic BMMSC-based therapy, which may have potential clinical applications for treating BRONJ.

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“…When macrophages were sensitized with bisphosphonates, chemokine production was suppressed (40). Bisphosphonates are also able to modulate the maturation of dendritic cells (41). These findings support an immunomodulatory effect of bisphosphonates.…”

Section: Preclinicalmentioning

confidence: 99%

Updates on osteonecrosis of the jaw

Yamashita

McCauley

Poznak

2010

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of review-Osteonecrosis of the Jaw (ONJ) in an uncommon condition noted to occur in patients with cancer receiving intravenous bisphosphonates. The etiology of ONJ remains unknown. The leading hypotheses addressing the mechanism of ONJ are reviewed here.Recent findings-The present clinical data suggests that ONJ may occur in approximately 5% of patients with metastatic bone disease. The ability to predict an individual's risk of developing ONJ remains elusive. It is likely that an altered bone microenvironment and/or host defense mechanisms effected by medications used to treat patients with metastatic bone disease contributes to the development of ONJ. Medications that significantly reduce osteoclastic activity are associated with ONJ. Preclinical models of ONJ are being developed, but to establish such an intricate systemic condition in animals is challenging.Summary-The ONJ field has progressed via knowledge gained by case reports, population-based studies and emerging animal models. Still, there are myths that need to be resolved and important clues that need to be investigated. Understanding the pathophysiology of this condition will be critical to improve patient care. Communications between oncologists, dentists, basic scientists and patients are central to effective treatment and research for this condition.

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Zoledronic acid, an aminobisphosphonate, modulates differentiation and maturation of human dendritic cells

Cited by 19 publications

References 35 publications

Zoledronic acid impairs myeloid differentiation to tumour-associated macrophages in mesothelioma

Zoledronic acid impairs myeloid differentiation to tumour-associated macrophages in mesothelioma

Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine

Updates on osteonecrosis of the jaw

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