Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss

Hoque, Jiaul; Shih, Yu‐Ru V.; Zeng, Yuze; Newman, Hunter; Sangaj, Nivedita; Arjunji, Neha; Varghese, Shyni

doi:10.1016/j.biomaterials.2021.120819

Cited by 33 publications

(38 citation statements)

References 55 publications

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“…Purine cascade contributes to maintain the differentiation capacity of MSCs into mature and functional osteoblasts ( Noronha-Matos and Correia-de-Sá, 2016 ). Adenosine is an important part of this pathway and plays a key role in maintaining bone health via activation of specific cell surface G protein coupled receptors (A1, A2A, A2B, and A3), and proteins ( Mediero and Cronstein, 2013 ; Hoque et al., 2021 ). The regulation of adenosine on both osteoclasts and osteoblasts varies with the dose.…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota and Serum Metabolic Signatures of High-Fat-Induced Bone Loss in Mice

Tang

Jiao

et al. 2021

Front. Cell. Infect. Microbiol.

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BackgroundAccumulating evidence indicates that high-fat diet (HFD) is a controllable risk factor for osteoporosis, but the underlying mechanism remains to be elucidated. As a primary biological barrier for nutrient entry into the human body, the composition and function of gut microbiota (GM) can be altered rapidly by HFD, which may trigger abnormal bone metabolism. In the current study, we analyzed the signatures of GM and serum metabolomics in HFD-induced bone loss and explored the potential correlations of GM and serum metabolites on HFD-related bone loss.MethodsWe conducted a mouse model with HFD-induced bone loss through a 12-week diet intervention. Micro-CT, Osmium-μCT, and histological analyses were used to observe bone microstructure and bone marrow adipose tissue. Quantitative Real-Time PCR was applied to analyze gene expression related to osteogenesis, adipogenesis, and osteoclastogenesis. Enzyme-linked immunosorbent assay was used to measure the biochemical markers of bone turnover. 16s rDNA sequencing was employed to analyze the abundance of GM, and UHPLC-MS/MS was used to identify serum metabolites. Correlation analysis was performed to explore the relationships among bone phenotypes, GM, and the metabolome.ResultsHFD induced bone loss accompanied by bone marrow adipose tissue expansion and bone formation inhibition. In the HFD group, the relative abundance of Firmicutes was increased significantly, while Bacteroidetes, Actinobacteria, Epsilonbacteraeota, and Patescibacteria were decreased compared with the ND group. Association analysis showed that thirty-two bacterial genera were significantly related to bone volume per tissue volume (BV/TV). One hundred and forty-five serum metabolites were identified as differential metabolites associated with HFD intervention, which were significantly enriched in five pathways, such as purine metabolism, regulation of lipolysis in adipocyte and cGMP-PKG signaling pathway. Sixty-four diffiential metabolites were matched to the MS2 spectra; and ten of them were positively correlated with BV/TV and five were negatively correlated with BV/TV.ConclusionsThese findings indicated that the alternations of GM and serum metabolites were related to HFD-induced bone loss, which might provide new insights into explain the occurrence and development of HFD-related osteoporosis. The regulatory effects of GM and metabolites associated with HFD on bone homeostasis required further exploration.

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Section: Discussionmentioning

confidence: 99%

Gut Microbiota and Serum Metabolic Signatures of High-Fat-Induced Bone Loss in Mice

Tang

Jiao

et al. 2021

Front. Cell. Infect. Microbiol.

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“…We considered that IONPs might have a synergetic effect with bisphosphonates in the aspect of POP treatment. Thus, we chose a common anti-OP drug, alendronate, as the bone targeting moiety [ 23 ]. Although the application of bisphosphonates could provide a satisfying therapeutic effect, the side effects caused by treatment, including atypical fracture, nephrotoxicity, and mandibular osteonecrosis, still represent a significant problem [ [45] , [46] , [47] ].…”

Section: Discussionmentioning

confidence: 99%

“…In present, delivery of nanomaterials to bone tissue remains challenging (low specificity and low clearance), limiting its application in clinical practice [ 21 ]. Previous studies demonstrated that phosphate radicals had the ability to be enriched in the bone surface [ [22] , [23] , [24] ]. In this study, we designed and synthesized a new bone targeting IONPs (BTNPs) loaded with a Food and Drug Administration (FDA) approved bisphosphonate, alendronate.…”

Section: Introductionmentioning

confidence: 99%

Bone targeting antioxidative nano-iron oxide for treating postmenopausal osteoporosis

Zheng

Zhuang

et al. 2022

Bioactive Materials

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“…Enhancing drug half-life and reducing the possibility of off-targeting are essential objectives in the development of bone-targeted nanosystems, Hoque et al modified hyaluronic acid methacrylate (HA-MA) by introducing Aln molecules via coupling reaction, and the obtained nanocarriers were loaded with adenosine molecules by dialysis. In vivo imaging system (IVIS) results showed that there was higher aggregation in bone tissue after systemic administration of Aln-ND, and it had a therapeutic effect in promoting bone formation and delaying bone loss in an ovariectomized model of osteoporotic mice ( Hoque et al, 2021 ).…”

Section: Bone-targeted Strategiesmentioning

confidence: 99%

Bone-Targeted Nanoparticle Drug Delivery System: An Emerging Strategy for Bone-Related Disease

Chen

et al. 2022

Front. Pharmacol.

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Targeted delivery by either systemic or local targeting of therapeutics to the bone is an attractive treatment for various bone metabolism diseases such as osteoporosis, osteoarthritis, osteosarcoma, osteomyelitis, etc. To overcome the limitations of direct drug delivery, the combination of bone-targeted agents with nanotechnology has the opportunity to provide a more effective therapeutic approach, where engineered nanoparticles cause the drug to accumulate in the bone, thereby improving efficacy and minimizing side effects. Here, we summarize the current advances in systemic or local bone-targeting approaches and nanosystem applications in bone diseases, which may provide new insights into nanocarrier-delivered drugs for the targeted treatment of bone diseases. We envision that novel drug delivery carriers developed based on nanotechnology will be a potential vehicle for the treatment of currently incurable bone diseases and are expected to be translated into clinical applications.

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Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss

Cited by 33 publications

References 55 publications

Gut Microbiota and Serum Metabolic Signatures of High-Fat-Induced Bone Loss in Mice

Gut Microbiota and Serum Metabolic Signatures of High-Fat-Induced Bone Loss in Mice

Bone targeting antioxidative nano-iron oxide for treating postmenopausal osteoporosis

Bone-Targeted Nanoparticle Drug Delivery System: An Emerging Strategy for Bone-Related Disease

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