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Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo

机译:Hesperidin促进骨肉内发生并在体外和体内调节胶原蛋白组织和矿化

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摘要

This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin’s influence in mineralized tissue formation and regeneration. Hesperidin was added to a culture of MC3T3-E1 cells at various concentrations. Cell proliferation, viability, osteogenic gene expression and deposited collagen matrix analyses were performed. Treatment with hesperidin showed significant upregulation of osteogenic markers, particularly with lower doses. Mature and compact collagen fibrils in hesperidin-treated cultures were observed by picrosirius red staining (PSR), although a thinner matrix layer was present for the higher dose of hesperidin compared to osteogenic media alone. Fourier-transform infrared spectroscopy indicated a better mineral-to-matrix ratio and matrix distribution in cultures exposed to hesperidin and confirmed less collagen deposited with the 100-µM dose of hesperidin. In vivo, hesperidin combined with a suboptimal dose of bone morphogenetic protein 2 (BMP2) (dose unable to promote healing of a rat mandible critical-sized bone defect) in a collagenous scaffold promoted a well-controlled (not ectopic) pattern of bone formation as compared to a large dose of BMP2 (previously defined as optimal in healing the critical-sized defect, although of ectopic nature). PSR staining of newly formed bone demonstrated that hesperidin can promote maturation of bone organic matrix. Our findings show, for the first time, that hesperidin has a modulatory role in mineralized tissue formation via not only osteoblast cell differentiation but also matrix organization and matrix-to-mineral ratio and could be a potential adjunct in regenerative bone therapies.
机译:本研究评估了植物化学,橙皮素,对骨质细胞功能和骨质形成和胶原基质质量的直接作用,因为关于哈培蛋白对矿化组织形成和再生的影响几乎没有着名。在各种浓度下加入Hesperidin至MC3T3-E1细胞的培养物中。进行细胞增殖,活力,成骨基因表达和沉积的胶原基质分析。用橙皮蛋白的处理表明,骨质原性标志物显着上调,特别是较低剂量。通过Picrosirius红染色(PSR)观察到Hemerperidin处理培养物中成熟和紧凑的胶原型原纤维,但是对于单独的骨质发生介质相比,存在较薄的矩阵层,尤其是橙皮蛋白的较高剂量。傅里叶变换红外光谱表明,暴露于橙皮素的培养物中的更好的矿物质与基质比和基质分布,并确认沉积100μm的橙皮素的胶原蛋白。在体内,Hesperidin结合了骨髓形态发生蛋白2(BMP2)的次优剂量剂量(BMP2)(剂量无法促进大鼠颌骨临界骨缺损的愈合),促进了良好控制的(非异位)模式的骨形成与大剂量的BMP2相比(先前定义为愈合临界缺陷时最佳,尽管异位性质)。新形成的骨骼的PSR染色证明橙皮素可以促进骨有机基质的成熟。我们的研究结果首次展示伊斯兰霉素在矿化组织形成中,不仅通过成骨细胞分化,还具有基质组织和基质到矿物比,并且可以是再生骨疗法的潜在辅助剂。

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