Bone resorption and remodeling in murine collagenase-induced osteoarthritis after administration of glucosamine.
Bone resorption and remodeling in murine collagenase-induced osteoarthritis after administration of glucosamine.
复制标题
服用氨基葡萄糖后，胶原酶诱导的小鼠骨关节炎的骨吸收和重塑。
DOI：
10.1186/ar3283
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发表时间：
2011-03-16
影响因子：
4.9
通讯作者：
Dimitrova P
中科院分区：
文献类型：
--
作者：
Ivanovska N;Dimitrova P
葡萄糖胺是一种氨基单糖，是糖胺聚糖的前体，是关节软骨的主要成分。葡萄糖胺已在临床上用于治疗骨关节炎，但其保护作用的数据是不足的。本研究的目的是探讨长期给药氨基葡萄糖对骨吸收和骨重塑的影响。在胶原酶诱导骨关节炎（CIOA）模型中研究了氨基葡萄糖对骨吸收和骨重塑的影响。采用酶联免疫吸附试验（ELISA）检测滑膜液中巨噬细胞炎性蛋白(MIP)-1α、活化调节蛋白、正常t细胞表达和分泌（RANTES）、核因子κ b配体可溶性受体激活物（RANKL）、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、4和10的水平。用流式细胞术分析了滑膜提取物中细胞群的变化以及肿瘤坏死因子α (TNF-α r)和干扰素γ (IFN-γR)受体在分化（CD） 3个阳性T细胞簇上的RANKL表达。采用免疫组化方法检测CIOA关节组织中转化生长因子(TGF)-β3、骨形态发生蛋白(BMP)-2、抗十肢瘫痪同源物2磷酸化蛋白母（pSMAD-2）、RANKL和Dickkopf-1蛋白（DKK-1）阳性染色。盐酸氨基葡萄糖能抑制CIOA小鼠软骨中糖胺聚糖（GAGs）和蛋白聚糖（pg）的丢失、骨侵蚀和骨赘的形成。降低CIOA关节液中可溶性RANKL和IL-6水平，诱导IL-10升高。葡萄糖胺限制了关节提取物中CD11b阳性Ly6G中性粒细胞和RANKL阳性CD3 T细胞的数量。通过下调RANKL表达抑制骨吸收，通过降低BMP-2、TGF-β3、pSMAD-2表达，上调DKK-1关节水平，影响CIOA骨重塑。我们的数据表明，盐酸氨基葡萄糖通过降低关节提取物中RANKL阳性CD3 T细胞的数量和sRANKL的水平，从而下调RANKL在关节中的表达，从而抑制骨吸收。葡萄糖胺的这些作用似乎对CIOA的进展至关重要，并导致关节骨重塑受限。
Glucosamine is an amino-monosaccharide and precursor of glycosaminoglycans, major components of joint cartilage. Glucosamine has been clinically introduced for the treatment of osteoarthritis but the data about its protective role in disease are insufficient. The goal of this study was to investigate the effect of long term administration of glucosamine on bone resorption and remodeling. The effect of glucosamine on bone resorption and remodeling was studied in a model of collagenase-induced osteoarthritis (CIOA). The levels of macrophage-inflammatory protein (MIP)-1α, protein regulated upon activation, normal T-cell expressed, and secreted (RANTES), soluble receptor activator of nuclear factor kappa-B ligand (RANKL), tumor necrosis factor (TNF)-α, and interleukin (IL)-6, 4 and 10 in synovial fluid were measured by enzyme-linked immunosorbent assay (ELISA). Cell populations in synovial extracts and the expression of RANKL, of receptors for TNF-α (TNF-αR) and interferon γ (IFN-γR) on clusters of differentiation (CD) three positive T cells were analyzed by flow cytometry. Transforming growth factor (TGF)-β3, bone morphogenetic protein (BMP)-2, phosphorylated protein mothers against decapentaplegic homolog 2 (pSMAD-2), RANKL and Dickkopf-1 protein (DKK-1) positive staining in CIOA joints were determined by immunohistochemistry. The administration of glucosamine hydrochloride in CIOA mice inhibited loss of glycosaminoglycans (GAGs) and proteoglycans (PGs) in cartilage, bone erosion and osteophyte formation. It decreased the levels of soluble RANKL and IL-6 and induced IL-10 increase in the CIOA joint fluids. Glucosamine limited the number of CD11b positive Ly6G neutrophils and RANKL positive CD3 T cells in the joint extracts. It suppressed bone resorption via down-regulation of RANKL expression and affected bone remodeling in CIOA by decreasing BMP-2, TGF-β3 and pSMAD-2 expression and up-regulating DKK-1 joint levels. Our data suggest that glucosamine hydrochloride inhibits bone resorption through down-regulation of RANKL expression in the joints, via reduction of the number of RANKL positive CD3 T cells and the level of sRANKL in the joints extracts. These effects of glucosamine appear to be critical for the progression of CIOA and result in limited bone remodeling of the joints.
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影响因子：
4.9
作者：
Bondeson J;Wainwright SD;Lauder S;Amos N;Hughes CE
通讯作者：
Hughes CE
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3.5
作者：
Gouze, JN;Bianchi, A;Bordji, K
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Bordji, K
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27.4
作者：
Boegard, T;Rudling, O;Jonsson, K
通讯作者：
Jonsson, K
影响因子：
27.4
作者：
Davidson, E. N. Blaney;Vitters, E. L.;van den Berg, W. B.
通讯作者：
van den Berg, W. B.
影响因子：
4.8
作者：
Ikeda, T;Kasai, M;Hirokawa, K
通讯作者：
Hirokawa, K