Gold Clusters Prevent Inflammation-Induced Bone Erosion through Inhibiting the Activation of NF-κB Pathway

Yuan, Qing; Gao, Fuping; Yao, Yawen; Cai, Pengju; Zhang, Xiangchun; Yuan, Jing; Hou, Kaixiao; Gao, Liang; Ren, Xiaojun; Gao, Xueyun

doi:10.7150/thno.31893

Cited by 36 publications

(29 citation statements)

References 36 publications

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“…An interesting question for future investigations would be whether the Pro-B cells can transdifferentiate to osteoclasts in the absence of monocytes, and whether this process is affected by inflammatory conditions which are known to stimulate osteoclastogenesis 57 , 58 . In our primary cultures, we could trace the differentiation of B cells to osteoclasts, but we cannot completely rule out the possibility that sporadic monocytes that did not reach the level of detection by flow cytometry were still present.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin receptor in B cells plays a role in bone remodeling in mice

Deshet-Unger¹,

Kim²,

Ben‐Califa³

et al. 2020

Theranostics

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Erythropoietin (EPO) is a key regulator of erythropoiesis. However, EPO receptors (EPO-Rs) are also expressed on non-erythroid cell types, including myeloid and bone cells. Immune cells also participate in bone homeostasis. B cells produce receptor activator of nuclear factor kappa-Β ligand (RANKL) and osteoprotegerin (OPG), two pivotal regulators of bone metabolism. Here we explored the ability of B cells to transdifferentiate into functional osteoclasts and examined the role of EPO in this process in a murine model. Methods: We have combined specifically-designed experimental mouse models and in vitro based osteoclastogenesis assays, as well as PCR analysis of gene expression. Results: (i) EPO treatment in vivo increased RANKL expression in bone marrow (BM) B cells, suggesting a paracrine effect on osteoclastogenesis; (ii) B cell-derived osteoclastogenesis occured in vivo and in vitro, as demonstrated by B cell lineage tracing in murine models; (iii) B-cell-derived osteoclastogenesis in vitro was restricted to Pro-B cells expressing CD115/CSF1-R and is enhanced by EPO; (iv) EPO treatment increased the number of B-cell-derived preosteoclasts (β3 + CD115 + ), suggesting a physiological rationale for B cell derived osteoclastogenesis; (v) finally, mice with conditional EPO-R knockdown in the B cell lineage (cKD) displayed a higher cortical and trabecular bone mass. Moreover, cKD displayed attenuated EPO-driven trabecular bone loss, an effect that was observed despite the fact that cKD mice attained higher hemoglobin levels following EPO treatment. Conclusions: Our work highlights B cells as an important extra-erythropoietic target of EPO-EPO-R signaling and suggests their involvement in the regulation of bone homeostasis and possibly in EPO-stimulated erythropoietic response. Importantly, we present here for the first time, histological evidence for B cell-derived osteoclastogenesis in vivo .

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Section: Discussionmentioning

confidence: 99%

Erythropoietin receptor in B cells plays a role in bone remodeling in mice

Deshet-Unger¹,

Kim²,

Ben‐Califa³

et al. 2020

Theranostics

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“…As a result, the Au cluster may provide an alternative to traditional antirheumatic drugs with more effectiveness and safety. 16,17…”

Section: Introductionmentioning

confidence: 99%

Dose-Dependent Efficacy of Gold Clusters on Rheumatoid Arthritis Therapy

et al. 2019

Self Cite

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Chronic inflammation and progressive bone damage in joints are two main pathological features of rheumatoid arthritis (RA). We have synthesized a gold cluster with glutathione (Au 29 SG 27 ) (named GA) that can effectively suppress both inflammation and bone damage in collagen-induced arthritis (CIA) in rats. Thus, gold clusters showed great potential for the therapy of RA. However, the optimal therapeutic dose remaining has to be determined. Therapeutic effect and safety are largely relying on drug dosage. Specifying the dose-dependent effects of GA on both therapy and biosafety can facilitate its clinical transformation research. Therefore, in this study, we comprehensively evaluated the dose-dependent efficacy of GA on the 30-day toxicity and RA treatment in rats. Results showed that continuous intraperitoneal injection of GA at a dose of 15 mg/kg (Au content) for 30 days resulted in slight hematological abnormalities and increases on organ coefficients of kidney and adrenal gland, while 10 mg Au/kg did not cause any obvious toxicity and side effects. In the treatment of CIA rats, only when the dose of GA reached 5 mg Au/kg, the symptoms of RA could be significantly improved. With regard to the histopathological analysis, although a lower dose of GA can suppress inflammation and bone damage to some extent, only the 5 mg Au/kg treatment could restore them to a state close to the normal control group. Therefore, we infer that 5 mg Au/kg is the optimal dose of GA for RA therapy in rats, which provides a theoretical basis for further preclinical research.

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“…[101] A recent study using a CIA model found that a peptide-coated gold cluster exerted antiinflammatory and anti-osteoclastogenesis effects via nuclear factor kappa-B (NF-κB) inhibition. [102] Biomimetic folate-chitosan-DNA NPs also decreased the osteoclast population in the AIA model by regulating osteocalcin, alkaline phosphatase, and tartrate-resistant acid phosphatase. [103] Song et al recently found that vascular EC-secreted exosomes not only presented more effective bone targeting than other cell-derived exosomes, but also inhibited osteoclast formation via its endogenous cargo miR-155.…”

Section: Osteoclastmentioning

confidence: 98%

Biomimetic and Bioinspired Intervention Strategies for the Treatment of Rheumatoid Arthritis

Han

Pang

2021

Adv Funct Materials

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Rheumatoid arthritis (RA) affects the joints and extra-articular organs and poses a significant health care problem in the modern era. Although current standard treatment modalities successfully control RA flares, no curative treatment modality for RA has been developed. Nanomedicines have addressed the drug side effects and limited efficacy of RA treatment. However, synthetic nanoparticles (NPs) can be toxic and induce immune responses in vivo, posing a risk of further RA progression. Biomimetic nanodrug delivery systems have the potential to improve the biocompatibility of synthetic NPs and the stability and targeting of pharmaceuticals in vivo. For many immune-related diseases with a complex pathogenesis and that involve a large number of different cell types, biomimetic nanodelivery systems can reduce the immunogenicity of NPs. Furthermore, some bioinspired strategies can mimic certain components of the pathological process, allowing for a more precise drug delivery and effective disease control via the carriers. This article highlights recent research on biomimetic nanodelivery systems for the treatment of RA and categorizes the design methodologies for various targets and carriers.

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Gold Clusters Prevent Inflammation-Induced Bone Erosion through Inhibiting the Activation of NF-κB Pathway

Cited by 36 publications

References 36 publications

Erythropoietin receptor in B cells plays a role in bone remodeling in mice

Erythropoietin receptor in B cells plays a role in bone remodeling in mice

Dose-Dependent Efficacy of Gold Clusters on Rheumatoid Arthritis Therapy

Biomimetic and Bioinspired Intervention Strategies for the Treatment of Rheumatoid Arthritis

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