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Effects of zinc and strontium substitution in tricalcium phosphate on osteoclast differentiation and resorption

机译:磷酸三钙中锌和锶替代对破骨细胞分化和吸收的影响

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Bone replacement materials must be able to regulate both osteoblastic synthesis of new bone and osteoclastic resorption process in order to maintain the balance of bone remodeling. Osteoclasts generate from differentiation of mononuclear cells. In the present study, we have studied osteoclast-like-cell responses (differentiation from mononuclear cells and resorption) to beta tricalcium phosphate (β-TCP) doped with zinc (Zn) and strontium (Sr). Osteoclast-like-cell differentiation and resorption was studied in vitro using an osteoclast-like-cell precursor RAW 264.7 cell, supplemented with receptor activator of nuclear factor κβ ligand (RANKL). Morphological and immunohistochemical analysis confirmed successful differentiation of the osteoclast-like-cells on the doped and undoped β-TCP substrates after 8 days of culture. Cells on the substrate surface expressed specific osteoclast markers such as; actin rings, multiple nuclei, tartrate-resistant acid phosphatase (TRAP) synthesis, and vitronectin receptors. However, quantitative TRAP assay indicated the inhibitory effect of Zn on osteoclast differentiation. Although, Zn doped β-TCP restricted osteoclast-like-cell differentiation, the samples were resorbed much faster. An increased resorption pit volume was noticed on Zn doped β-TCP samples after 28 days of culture compared to pure and Sr doped β-TCP. In this work, we demonstrated that β-TCP bone substitute materials can be successfully resorbed by osteoclast-like-cells, where both osteoclast-like-cell differentiation and resorption were modulated by Zn and/or Sr doping - a much needed property for successful bone remodeling.
机译:骨替代材料必须能够调节新骨的成骨细胞合成和破骨细胞吸收过程,以维持骨重塑的平衡。破骨细胞由单核细胞分化产生。在本研究中,我们研究了破骨细胞样细胞对单核细胞的分化和再吸收对掺杂锌(Zn)和锶(Sr)的β-磷酸三钙(β-TCP)的反应。使用破骨细胞样细胞前体RAW 264.7细胞和核因子κβ配体的受体激活剂(RANKL)进行了体外研究,研究了破骨细胞样细胞的分化和吸收。形态和免疫组织化学分析证实,培养8天后,掺杂和未掺杂的β-TCP基质上破骨细胞样细胞成功分化。基质表面上的细胞表达特定的破骨细胞标记,例如;肌动蛋白环,多核,抗酒石酸酸性磷酸酶(TRAP)合成和玻连蛋白受体。然而,定量TRAP分析表明锌对破骨细胞分化的抑制作用。尽管锌掺杂的β-TCP限制了破骨细胞样细胞的分化,但样品的吸收速度更快。与纯净和Sr掺杂的β-TCP相比,培养28天后,Zn掺杂的β-TCP样品的吸收坑体积增加。在这项工作中,我们证明了β-TCP骨替代材料可以被破骨细胞样细胞成功吸收,其中破骨细胞样细胞的分化和吸收均受Zn和/或Sr掺杂的调节,这是成功获得成功的必要条件骨骼重塑。

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