Cytokine-scavenging nanodecoys reconstruct osteoclast/osteoblast balance toward the treatment of postmenopausal osteoporosis

Yang, Zhou; Deng, Yekun; Liu, Zhongmin; Yin, Mengyuan; Hou, Mengying; Zhao, Zhi‐Wen; Zhou, Xiaozhong; Yin, Lichen

doi:10.1126/sciadv.abl6432

Cited by 65 publications

(48 citation statements)

References 59 publications

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“…ZIA is an acute inflammatory arthritis model which involves both acute inflammation and excessive T cell activation [ 18b,19a,26 ] It will cause severe tissue damage, and thus it is important to reduce inflammation quickly and effectively. We first determined the anti‐inflammatory efficacy of PRM NDs in ZIA mice by monitoring the expression levels of pro‐inflammatory cytokines in the synovium tissues of ZIA mice at day 6 post i.v.…”

Section: Resultsmentioning

confidence: 99%

Immuno‐Engineered Nanodecoys for the Multi‐Target Anti‐Inflammatory Treatment of Autoimmune Diseases

et al. 2022

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Overactivated T cells and overproduced pro‐inflammatory cytokines form a self‐amplified signaling loop to continuously exacerbate the dysregulated inflammatory response and propel the progression of autoimmune diseases (AIDs). Herein, immuno‐engineered nanodecoys (NDs) based on poly(lactic‐co‐glycolic acid) nanoparticles coated with programmed death‐ligand 1 (PD‐L1)‐expressing macrophage membrane (PRM) are developed to mediate multi‐target interruption of the self‐promoted inflammatory cascade in AIDs. The PRM collected from IFN‐γ‐treated RAW 264.7 cells possesses elevated surface levels of adhesion molecule receptors and pro‐inflammatory cytokine receptors, and, thus, systemically administered PRM NDs afford higher accumulation level in inflamed tissues and stronger scavenging efficiency toward multiple pro‐inflammatory cytokines. More importantly, IFN‐γ treatment induces remarkable PD‐L1 expression on PRM, thereby allowing PRM NDs to bind membrane‐bound programmed death‐1 (PD‐1) on CD4+ T cell surfaces or neutralize free soluble PD‐1, which reconstructs the PD‐1/PD‐L1 inhibitory axis to suppress CD4+ T cell activation and restore immune tolerance. As such, PRM NDs provoke potent and cooperative anti‐inflammatory and immune‐suppressive efficacies to alleviate autoimmune damages in Zymosan A‐induced arthritis mice and dextran sulfate sodium‐induced ulcerative colitis mice. This study provides an enlightened example for the immuno‐engineering of cell‐membrane‐based NDs, rendering promising implications into the treatment of AIDs via multi‐target immune‐modulation.

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Section: Resultsmentioning

confidence: 99%

Immuno‐Engineered Nanodecoys for the Multi‐Target Anti‐Inflammatory Treatment of Autoimmune Diseases

et al. 2022

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“…Given the multifunctional effects of bioactive ions reported to comodulate the pro-osteogenic and anti-osteoclastogenic healing processes 18 , 20 , 49 – 51 and the previously reported role of Mo in promoting periodontal regeneration, 29 in this study, we further investigated the therapeutic effect of Mo ions from the standpoint of orchestrating the cellular responses of osteoblasts and osteoclasts using in vitro and in vivo models. Previously, we found that a strut-packed Mo-containing bioactive glass ceramic scaffold with a hollow-pipe structure can promote periodontal wound healing; 29 however, the hollow-pipe structure can cause unnecessary infection due to the poor filling of newly formed bone.…”

Section: Discussionmentioning

confidence: 99%

A 3D-printed molybdenum-containing scaffold exerts dual pro-osteogenic and anti-osteoclastogenic effects to facilitate alveolar bone repair

Tian

Zhang

et al. 2022

Int J Oral Sci

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The positive regulation of bone-forming osteoblast activity and the negative feedback regulation of osteoclastic activity are equally important in strategies to achieve successful alveolar bone regeneration. Here, a molybdenum (Mo)-containing bioactive glass ceramic scaffold with solid-strut-packed structures (Mo-scaffold) was printed, and its ability to regulate pro-osteogenic and anti-osteoclastogenic cellular responses was evaluated in vitro and in vivo. We found that extracts derived from Mo-scaffold (Mo-extracts) strongly stimulated osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited differentiation of osteoclast progenitors. The identified comodulatory effect was further demonstrated to arise from Mo ions in the Mo-extract, wherein Mo ions suppressed osteoclastic differentiation by scavenging reactive oxygen species (ROS) and inhibiting mitochondrial biogenesis in osteoclasts. Consistent with the in vitro findings, the Mo-scaffold was found to significantly promote osteoblast-mediated bone formation and inhibit osteoclast-mediated bone resorption throughout the bone healing process, leading to enhanced bone regeneration. In combination with our previous finding that Mo ions participate in material-mediated immunomodulation, this study offers the new insight that Mo ions facilitate bone repair by comodulating the balance between bone formation and resorption. Our findings suggest that Mo ions are multifunctional cellular modulators that can potentially be used in biomaterial design and bone tissue engineering.

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“…at the first day of each week. Micro-CT analyses were described in an early study [ 70 ]. In brief, the OVX mice and the control mice were scanned under the micro-CT equipment (Skyscan 1176, Belgium) 8 weeks after OVX procedure and the high-resolution scanogram were retrieved [ 70 ].…”

Section: Methodsmentioning

confidence: 99%

“…Micro-CT analyses were described in an early study [ 70 ]. In brief, the OVX mice and the control mice were scanned under the micro-CT equipment (Skyscan 1176, Belgium) 8 weeks after OVX procedure and the high-resolution scanogram were retrieved [ 70 ]. The dataset was reconstructed under a CT analyzer software and bone erosion was calculated using the in-house Fiji script [ 70 ].…”

Section: Methodsmentioning

confidence: 99%

“…The trabecular bone volume (BV) versus the total volume (TV), in %, was measured. The bone mineral density (BMD, g/cm 3 ) of trabecular bones and cortical bones was calculated as well [ 70 ]. After completion of micro-CT, the right tibias of the mice were collected and superoxide dismutase (SOD) activity in the fresh bone tissues was analyzed by a SOD ELISA kit (Thermo-Fisher Invitrogen, Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

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Nrf2 signaling activation by a small molecule activator compound 16 inhibits hydrogen peroxide-induced oxidative injury and death in osteoblasts

et al. 2022

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We explored the potential activity of compound 16 (Cpd16), a novel small molecule Nrf2 activator, in hydrogen peroxide (H2O2)-stimulated osteoblasts. In the primary murine/human osteoblasts and MC3T3-E1 murine osteoblastic cells, Cpd16 treatment at micro-molar concentrations caused disassociation of Keap1-Nrf2 and Nrf2 cascade activation. Cpd16 induced stabilization of Nrf2 protein and its nuclear translocation, thereby increasing the antioxidant response elements (ARE) reporter activity and Nrf2 response genes transcription in murine and human osteoblasts. Significantly, Cpd16 mitigated oxidative injury in H2O2-stimulited osteoblasts. H2O2-provoked apoptosis as well as programmed necrosis in osteoblasts were significantly alleviated by the novel Nrf2 activator. Cpd16-induced Nrf2 activation and osteoblasts protection were stronger than other known Nrf2 activators. Dexamethasone- and nicotine-caused oxidative stress and death in osteoblasts were attenuated by Cpd16 as well. Cpd16-induced osteoblast cytoprotection was abolished by Nrf2 short hairpin RNA or knockout, but was mimicked by Keap1 knockout. Keap1 Cys151S mutation abolished Cpd16-induced Nrf2 cascade activation and osteoblasts protection against H2O2. Importantly, weekly Cpd16 administration largely ameliorated trabecular bone loss in ovariectomy mice. Together, Cpd16 alleviates H2O2-induced oxidative stress and death in osteoblasts by activating Nrf2 cascade.

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Cytokine-scavenging nanodecoys reconstruct osteoclast/osteoblast balance toward the treatment of postmenopausal osteoporosis

Abstract: Biomimetic nanodecoys reconstruct the osteoclast/osteoblast balance to treat postmenopausal osteoporosis.

Cited by 65 publications

References 59 publications

Immuno‐Engineered Nanodecoys for the Multi‐Target Anti‐Inflammatory Treatment of Autoimmune Diseases

Immuno‐Engineered Nanodecoys for the Multi‐Target Anti‐Inflammatory Treatment of Autoimmune Diseases

A 3D-printed molybdenum-containing scaffold exerts dual pro-osteogenic and anti-osteoclastogenic effects to facilitate alveolar bone repair

Nrf2 signaling activation by a small molecule activator compound 16 inhibits hydrogen peroxide-induced oxidative injury and death in osteoblasts

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