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骨转换异常的调节:实验性大鼠模型中原发性骨质疏松症治疗的一个靶点。

Modulation of bone turnover aberration: A target for management of primary osteoporosis in experimental rat model.

作者信息

Fouad-Elhady Enas A, Aglan Hadeer A, Hassan Rasha E, Ahmed Hanaa H, Sabry Gilane M

机构信息

Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.

Hormones Department, Medical Research Division, National Research Centre, Giza, Egypt.

出版信息

Heliyon. 2020 Feb 6;6(2):e03341. doi: 10.1016/j.heliyon.2020.e03341. eCollection 2020 Feb.

Abstract

Osteoporosis is a skeletal degenerative disease characterised by abnormal bone turnover with scant bone formation and overabundant bone resorption. The present approach was intended to address the potency of nanohydroxyapatite (nHA), chitosan/hydroxyapatite nanocomposites (nCh/HA) and silver/hydroxyapatite nanoparticles (nAg/HA) to modulate bone turnover deviation in primary osteoporosis induced in the experimental model. Characterisation techniques such as TEM, zeta-potential, FT-IR and XRD were used to assess the morphology, the physical as well as the chemical features of the prepared nanostructures. The experiment was conducted on forty-eight adult female rats, randomised into 6 groups (8 rats/group), (1) gonad-intact, (2) osteoporotic group, (3) osteoporotic + nHA, (4) osteoporotic + nCh/HA, (5) osteoporotic + nAg/HA and (6) osteoporotic + alendronate (ALN). After three months of treatment, serum sclerostin (SOST), bone alkaline phosphatase (BALP) and bone sialoprotein (BSP) levels were quantified using ELISA. Femur bone receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) and cathepsin K (CtsK) mRNA levels were evaluated by quantitative RT-PCR. Moreover, alizarin red S staining was applied to determine the mineralisation intensity of femur bone. Findings in the present study indicated that treatment with nHA, nCh/HA or nAg/HA leads to significant repression of serum SOST, BALP and BSP levels parallel to a significant down-regulation of RANKL and CtsK gene expression levels. On the other side, significant enhancement in the calcification intensity of femur bone has been noticed. The outcomes of this experimental setting ascertained the potentiality of nHA, nCh/HA and nAg/HA as promising nanomaterials in attenuating the excessive bone turnover in the primary osteoporotic rat model. The mechanisms behind the efficacy of the investigated nanostructures involved the obstacle of serum and tissue indices of bone resorption besides the strengthening of bone mineralisation.

摘要

骨质疏松症是一种骨骼退行性疾病,其特征是骨转换异常,骨形成不足而骨吸收过度。本研究旨在探讨纳米羟基磷灰石(nHA)、壳聚糖/羟基磷灰石纳米复合材料(nCh/HA)和银/羟基磷灰石纳米颗粒(nAg/HA)调节实验模型中原发性骨质疏松症骨转换偏差的效能。采用透射电子显微镜(TEM)、zeta电位、傅里叶变换红外光谱(FT-IR)和X射线衍射(XRD)等表征技术评估所制备纳米结构的形态、物理和化学特性。实验选用48只成年雌性大鼠,随机分为6组(每组8只):(1)性腺完整组;(2)骨质疏松组;(3)骨质疏松+nHA组;(4)骨质疏松+nCh/HA组;(5)骨质疏松+nAg/HA组;(6)骨质疏松+阿仑膦酸钠(ALN)组。治疗三个月后,采用酶联免疫吸附测定(ELISA)法测定血清硬化蛋白(SOST)、骨碱性磷酸酶(BALP)和骨唾液蛋白(BSP)水平。通过定量逆转录聚合酶链反应(RT-PCR)评估股骨核因子-κB(NF-κB)配体(RANKL)和组织蛋白酶K(CtsK)的mRNA水平。此外,采用茜素红S染色法测定股骨的矿化强度。本研究结果表明,nHA、nCh/HA或nAg/HA治疗可显著抑制血清SOST、BALP和BSP水平,同时显著下调RANKL和CtsK基因表达水平。另一方面,观察到股骨钙化强度显著增强。该实验结果证实了nHA、nCh/HA和nAg/HA作为有前景的纳米材料在减轻原发性骨质疏松大鼠模型中过度骨转换方面的潜力。所研究纳米结构疗效背后的机制包括抑制骨吸收的血清和组织指标以及增强骨矿化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b155/7011045/6c3f3d33848d/gr1.jpg

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