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Intra‐articular delivery of glucosamine for treatment of experimental osteoarthritis created by a medial meniscectomy in a rat model

机译:葡萄糖胺的关节腔内给药治疗大鼠半月板内侧半月板切除术引起的实验性骨关节炎

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摘要

Glucosamine (GlcN) is a naturally occurring amino-monosaccharide with putative chondroprotective activity. Optimum responses to GlcN are achieved at concentrations which are impractical with oral dosing. Intra-articular delivery of a bolus dose of GlcN is one way to overcome these pharmacokinetic obstacles. In this study we report the effects of exposing primary human chondrocytes to a bolus dose of GlcN. We also locally administered GlcN in the context of a meniscal transection model of rat osteoarthritis (OA). The knees of male rats were subjected to medial meniscal transection and developed arthritic changes over 4 weeks. Treatment groups were then given thrice weekly 100 μL injections of 35 μg, 350 μg, 1.8 mg, or 3.5 mg of GlcN dissolved in normal saline. Gross images, modified Mankin scores, and histomorphometric measurements were used as outcome measures. The 350 μg dosage of GlcN had the most significant positive impact on all components of the modified Mankin score. Together, these findings suggest the local delivery of high concentrations of GlcN is well tolerated and can suppress experimental OA through influences on both bone and cartilage.
机译:葡萄糖胺(GlcN)是具有推测的软骨保护活性的天然存在的氨基单糖。在口服给药不可行的浓度下可获得对GlcN的最佳反应。大剂量GlcN的关节内递送是克服这些药代动力学障碍的一种方法。在这项研究中,我们报告了将原代人软骨细胞暴露于大剂量GlcN的影响。我们还在大鼠骨关节炎(OA)的半月板横断模型的背景下局部施用GlcN。对雄性大鼠的膝盖进行半月板内侧横断,并在4周内出现关节炎变化。然后,每周给治疗组三次,分别注射溶于生理盐水中的35μg,350μg,1.8μmg或3.5μmg的GlcN100μL。总体图像,修改后的Mankin评分和组织形态计量学指标用作结果指标。 350μgGlcN剂量对改良的Mankin评分的所有组成部分具有最显着的积极影响。总之,这些发现表明,高浓度的GlcN的局部递送具有良好的耐受性,并且可以通过对骨骼和软骨的影响来抑制实验性OA。

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