Osteoporosis is a skeletal disorder resulted in significant structural and functional changes, arousing a wide concern for the high prevalence and cost. Imbalance between osteoclastogenesis and osteogenesis have been verified as a main pathology etiology and considered an efficient therapy target in both clinical and pre-clinical studies. In recent years, inorganic nanomaterials have shown provable activities on osteoclastogenesis inhibition and osteogenesis promotion, respectively. Hence, in this study, a class of hydroxyapatite coated superparamagnetic iron oxide nanoparticles (SPIO@HA) were developed with a core−shell structure for targeting both osteoclastogenesis and osteogenesis. The optimal ratio of SPIO@15HA (Fe/Ca = 1:15, mol/mol) was screened to obtain dual function for inducing both bone formation and preventing bone resorption. The obtained nanocomposites significantly prevented the bone loss of ovariectomized (OVX) mice and increased bone mineral density (BMD) by 9.4%, exhibiting high bone accumulation in magnetic resonance imaging evaluation and reasonable biosafety profile. The mechanism study revealed that SPIO@15HA can suppress bone marrow monocyte derived osteoclast differentiation through TRAF6−p62−CYLD signaling complex regulation. Meanwhile, it could activate MSC osteogenic differentiation by TGF-β, PI3K-AKT and calcium signaling pathway regulation. Moreover, incubation of SPIO@15HA with MSC resulted in several cytokines overexpression such as osteoprotegerin (OPG), CSF2, CCL2 etc., which are responsible for maintaining the bone remodeling balance. The dual function of as-prepared SPIO@15HA may find a new way for designing of inorganic components containing core/shell nanomaterials for osteoporosis treatment.

中文翻译：

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氧化铁羟基磷灰石核/壳纳米复合材料在骨质疏松症治疗中破骨细胞生成和成骨的双重调控

骨质疏松症是一种骨骼疾病，会导致显着的结构和功能变化，引起人们对高患病率和成本的广泛关注。破骨细胞生成和成骨之间的不平衡已被证实为主要的病理病因，并被认为是临床和临床前研究中的有效治疗靶点。近年来，无机纳米材料分别在破骨细胞生成抑制和成骨促进方面显示出可证明的活性。因此，在本研究中，开发了一类具有核壳结构的羟基磷灰石包覆的超顺磁性氧化铁纳米颗粒（SPIO@HA），用于靶向破骨细胞生成和成骨。筛选出SPIO@15HA的最佳配比(Fe/Ca = 1:15, mol/mol)以获得诱导骨形成和防止骨吸收的双重功能。所获得的纳米复合材料显着防止了去卵巢（OVX）小鼠的骨丢失，并使骨矿物质密度（BMD）增加了 9.4%，在磁共振成像评估中表现出高的骨积累和合理的生物安全性。机制研究表明，SPIO@15HA可以通过TRAF6-p62-CYLD信号复合物调控抑制骨髓单核细胞衍生的破骨细胞分化。同时通过TGF-β、PI3K-AKT和钙信号通路调控激活MSC成骨分化。此外，SPIO@15HA 与 MSC 的孵育导致几种细胞因子过表达，如骨保护素 (OPG)、CSF2、CCL2 等，它们负责维持骨重塑平衡。