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Bone targeting antioxidative nano-iron oxide for treating postmenopausal osteoporosis.

ABSTRACT: Osteoporosis is the most common degenerative orthopedic disease in the elderly. Recently, the therapeutic methods for osteoporosis have shifted towards the regulation of local immunity in bone tissues, which could provide a suitable environment for the positive regulation of bone metabolism, promoting osteogenic differentiation and inhibiting osteoclast differentiation. Our previous work demonstrated that iron oxide nanoparticles (IONPs) could positively regulate bone metabolism in vitro. In this study, we further demonstrated that daily administration of IONPs relieved estrogen deficiency-induced osteoporosis via scavenging reactive oxygen species in vivo. Meanwhile, IONPs promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited the osteoclast differentiation of monocytes from IONPs treated mice. Besides, alendronate, a clinically used anti-osteoporosis bisphosphate, was employed to precisely deliver the IONPs to the bone tissues and played a synergically therapeutic role. Eventually, we verified the bone targeting ability, therapeutic efficiency, and biocompatibility of the novel bone target iron oxides in ovariectomy-induced osteoporotic mice. By applying BTNPs, the OVX-induced osteoporosis was significantly revised in mice models via the positive regulation of bone metabolism.

SUBMITTER: Zheng L

PROVIDER: S-EPMC8897644 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Bone targeting antioxidative nano-iron oxide for treating postmenopausal osteoporosis.

Zheng Liming L Zhuang Zaikai Z Li Yixuan Y Shi Tianshu T Fu Kai K Yan Wenjin W Zhang Lei L Wang Peng P Li Lan L Jiang Qing Q

Bioactive materials 20211124

Osteoporosis is the most common degenerative orthopedic disease in the elderly. Recently, the therapeutic methods for osteoporosis have shifted towards the regulation of local immunity in bone tissues, which could provide a suitable environment for the positive regulation of bone metabolism, promoting osteogenic differentiation and inhibiting osteoclast differentiation. Our previous work demonstrated that iron oxide nanoparticles (IONPs) could positively regulate bone metabolism <i>in vitro</i>. ...[more]

PMID: 35310348

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Project description:ObjectivePostmenopausal osteoporosis (PMOP) is a common age-associated disease in the life course. Clinically, Xiaozeng Qianggu Tablets (XQT) have a potent therapeutic effect on the PMOP. However, the bioactive components and the mechanism of XQT underlying the PMOP treatment were unclear and it should be explored to discover the scientific connotation in traditional medical practice.MethodsThe components in XQT were identified by UPLC-Q-TOF/MS. The animal model of PMOP was established by surgical ovariectomy in the female Sprague-Dawley rats. After treatment of XQT, the therapeutic effect was assessed by the determination of bone metabolism biomarkers in serum and histopathological examination. The effect of XQT on the autophagy and bone micro-situation were tested using western blot, RT-qPCR, and transmission electron microscope.ResultsThere were 27 compounds identified in XQT, including catalpol, monotropein, verbascoside, cryptochlorogenic acid, 5,7-dihydroxychromone 7-rutinoside, biorobin, and so on. The bone metabolism markers (alkaline phosphatase, bone alkaline phosphatase, procollagen type I intact N-terminal propeptide, cross-linked carboxy-terminal telopeptide of type I collagen, and tartrate-resistant acid phosphatase) were significantly increased in the PMOP rats and reversed by XQT administration. Moreover, the width of bone trabeculae and the ratio of the area of calcium deposition to bone trabeculae were also improved after treating the middle dose of XQT. Meanwhile, the bone micro-structure was improved by XQT. The mRNA and protein expression of unc-51 like kinase 1, beclin-1, and microtubule-associated protein 1B-light chain 3 in PMOP rats were down-regulated and up-regulated by XQT administration.ConclusionsThe compounds in XQT, including catalpol, monotropein, verbascoside cryptochlorogenic acid, and so on, were valuable for further pharmacy evaluation. The pathological changes and bone micro-structure were improved by XQT, and the down-regulated autophagy level was also restored, which suggested a potent effect of XQT on treating PMOP, corresponding to its clinic use.

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Bone targeting antioxidative nano-iron oxide for treating postmenopausal osteoporosis.

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Bone targeting antioxidative nano-iron oxide for treating postmenopausal osteoporosis.

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