Dataset Information

Regulating Type H Vessel Formation and Bone Metabolism via Bone-Targeting Oral Micro/Nano-Hydrogel Microspheres to Prevent Bone Loss.

ABSTRACT: Postmenopausal osteoporosis is one of the most prevalent skeletal disorders in women and is featured by the imbalance between intraosseous vascularization and bone metabolism. In this study, a pH-responsive shell-core structured micro/nano-hydrogel microspheres loaded with polyhedral oligomeric silsesquioxane (POSS) using gas microfluidics and ionic cross-linking technology are developed. This micro/nano-hydrogel microsphere system (PDAP@Alg/Cs) can achieve oral delivery, intragastric protection, intestinal slow/controlled release, active targeting to bone tissue, and thus negatively affecting intraosseous angiogenesis and osteoclastogenesis. According to biodistribution data, PDAP@Alg/Cs can successfully enhance drug intestinal absorption and bioavailability through intestine adhesion and bone targeting after oral administration. In vitro and in vivo experiments reveal that PDAP@Alg/Cs promoted type H vessel formation and inhibited bone resorption, effectively mitigating bone loss by activating HIF-1α/VEGF signaling pathway and promoting heme oxygenase-1 (HO-1) expression. In conclusion, this novel oral micro/nano-hydrogel microsphere system can simultaneously accelerate intraosseous vascularization and decrease bone resorption, offering a brand-new approach to prevent postmenopausal osteoporosis.

SUBMITTER: Li J

PROVIDER: S-EPMC10214236 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Regulating Type H Vessel Formation and Bone Metabolism via Bone-Targeting Oral Micro/Nano-Hydrogel Microspheres to Prevent Bone Loss.

Li Junjie J Wei Gang G Liu Gongwen G Du Yawei Y Zhang Ruizhi R Wang Aifei A Liu Baoshan B Cui Wenguo W Jia Peng P Xu Youjia Y

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20230326 15

Postmenopausal osteoporosis is one of the most prevalent skeletal disorders in women and is featured by the imbalance between intraosseous vascularization and bone metabolism. In this study, a pH-responsive shell-core structured micro/nano-hydrogel microspheres loaded with polyhedral oligomeric silsesquioxane (POSS) using gas microfluidics and ionic cross-linking technology are developed. This micro/nano-hydrogel microsphere system (PDAP@Alg/Cs) can achieve oral delivery, intragastric protection ...[more]

PMID: 36967561

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Project description:Postmenopausal osteoporosis (PMOP) is an estrogen deficiency-induced bone loss, which has been shown an association with an altered gut microbiota (GM). Gut microbiota-bone axis has been recognized as a crucial mediator for bone homeostasis. Icariin (ICA) is an effective agent to delay bone loss by regulating the bone homeostasis. Thus, we hypothesize that ICA can prevent bone loss by modulating GM and regulating metabolite alterations. The effects of ICA on bone metabolism improvement in ovariectomized (OVX) rats and their relationships with the GM and fecal metabolites were investigated. Micro-computed tomography (micro-CT) and hematoxylin-eosin (HE) staining showed a typical bone boss in OVX group, while ICA or estradiol (E2) administration exhibited positive effects on bone micro-architecture improvement. The GM such as Actinobacteria, Gammaproteobacteria, Erysipelotrichi, Erysipelotrichales, Enterobacteriales, Actinomycetales, Ruminococcus and Oscillospira significantly correlated to serum bone Gla-protein (BGP), receptor activator of nuclear factor-κB (RANK), receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG) and tartrate resistant acid phosphatase (TRACP). Further t-test revealed a substantial variation of the GM and fecal metabolites in different treatments. Among them, Lachnoclostridium, Butyricimonas, Rikenella, Paraprevolla, Adlercreutzia, Enterorhabdus, Anaerovorax, Allobaculum, Elusimicrobium, Lactococcus, Globicatella and Lactobacillus were probably the key microbial communities driving the change of bile acid, amino acid and fatty acid, thereby leading to an improvement of PMOP. The significant up-regulation of L-Saccharopine, 1-Aminocyclohexadieneacid and linoleic acid after ICA administration suggested important contributions of amino acid and fatty acid metabolisms in the prevention and treatment of PMOP. Taken together, our study has provided new perspectives to better understand the effects of ICA on PMOP improvement by regulating GM and the associated fecal metabolites. Our findings contribute to develop ICA as a potential therapy for PMOP.

Dataset Information

Regulating Type H Vessel Formation and Bone Metabolism via Bone-Targeting Oral Micro/Nano-Hydrogel Microspheres to Prevent Bone Loss.

Publications

Regulating Type H Vessel Formation and Bone Metabolism via Bone-Targeting Oral Micro/Nano-Hydrogel Microspheres to Prevent Bone Loss.

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