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首页> 外文期刊>Osteoarthritis and cartilage >Glucosamine modulates chondrocyte proliferation, matrix synthesis, and gene expression.
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Glucosamine modulates chondrocyte proliferation, matrix synthesis, and gene expression.

机译:葡萄糖胺调节软骨细胞增殖,基质合成和基因表达。

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OBJECTIVE: To investigate the effects of glucosamine (GlcN) on chondrocyte proliferation, matrix production, and gene expression for providing insights into the biochemical basis of its reported beneficial effects in osteoarthritis (OA). METHODS: Dose-dependent effect of GlcN on cell morphology, proliferation, cartilage matrix production and gene expression was examined by incubating primary bovine chondrocytes with various amounts of GlcN in monolayers (2D) and in cell-laden hydrogels (3D constructs). Histology, immunofluorescent staining and biochemical analyses were used to determine the effect of GlcN on cartilage matrix production in 3D constructs. The impact of GlcN on gene expression was evaluated with real-time polymerase chain reaction (PCR). RESULTS: GlcN concentration and culture conditions significantly affected the cell behavior. Quantitative detection of matrix production in cell-laden hydrogels indicated a relatively narrow window of GlcN concentration that promotes matrix production (while limiting cellular proliferation, but not cell viability). Notably, GlcN enhanced cartilage specific matrix components, aggrecan and collagen type II, in a dose-dependent manner up to 2 mM but the effect was lost by 15 mM. Additionally, GlcN treatment up-regulated transforming growth factor-beta1 (TGF-beta1) mRNA levels. CONCLUSION: Results indicate that culture conditions play a significant role in determining the effect of GlcN on chondrocytes, explaining both the previously reported beneficial and deleterious effects of this sugar. The ability of GlcN to alter TGF-beta1 signaling provides a biochemical mechanism for GlcN activity on chondrocytes that up to now has remained elusive. The observed anabolic effect of optimal GlcN concentrations on chondrocytes may be useful in formulating effective cartilage repair strategies.
机译:目的:研究葡糖胺(GlcN)对软骨细胞增殖,基质产生和基因表达的影响,以期了解其报道的对骨关节炎(OA)有益作用的生物化学基础。方法:通过在单层(2D)和载有细胞的水凝胶(3D构建体)中孵育含有各种量的GlcN的原代牛软骨细胞,来研究GlcN对细胞形态,增殖,软骨基质产生和基因表达的剂量依赖性作用。使用组织学,免疫荧光染色和生化分析来确定GlcN对3D构建物中软骨基质产生的影响。使用实时聚合酶链反应(PCR)评估了GlcN对基因表达的影响。结果:GlcN浓度和培养条件显着影响细胞行为。载有细胞的水凝胶中基质产生的定量检测表明,GlcN浓度窗口相对较窄,可促进基质产生(同时限制细胞增殖,但不限制细胞活力)。值得注意的是,GlcN以剂量依赖的方式增强了软骨特定的基质成分,聚集蛋白聚糖和II型胶原,直至2 mM,但作用消失了15 mM。此外,GlcN治疗上调了转化生长因子-beta1(TGF-beta1)mRNA的水平。结论:结果表明培养条件在确定GlcN对软骨细胞的作用中起重要作用,解释了先前报道的这种糖的有益和有害作用。 GlcN改变TGF-beta1信号转导的能力为软骨细胞上的GlcN活性提供了一种生化机制,到目前为止,这种活性尚不清楚。观察到的最佳GlcN浓度对软骨细胞的合成代谢作用可能有助于制定有效的软骨修复策略。

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