What is the effect of nicotinic acetylcholine receptor stimulation on osteoarthritis in a rodent animal model?
What is the effect of nicotinic acetylcholine receptor stimulation on osteoarthritis in a rodent animal model?
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DOI：
10.1177/2050312116637529
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发表时间：
2016
影响因子：
2.3
通讯作者：
Claassen L
中科院分区：
文献类型：
--
作者：
Bock K;Plaass C;Coger V;Peck CT;Reimers K;Stukenborg-Colsman C;Claassen L
尽管骨关节炎患者数量不断增加，但尚未建立足够的骨关节炎软骨保护和预防性治疗。本研究的目的是验证通过尼古丁刺激烟碱乙酰胆碱受体是否对骨关节炎发展中的软骨退化具有有益作用，并且能够减少骨关节炎诱导后滑膜中促炎细胞因子和软骨降解酶的表达。在刘易斯大鼠中使用单碘乙酸盐的标准化骨关节炎模型诱导实验性骨关节炎。将16只刘易斯大鼠随机分为4组：对照组、假手术+尼古丁应用组、骨关节炎组和骨关节炎+尼古丁应用组。腹腔内给予尼古丁（0.625 mg/kg，每日两次），持续42天。我们通过定量聚合酶链反应分析了组织学切片、放射学图像和滑膜中促炎细胞因子（如白细胞介素-1 β、肿瘤坏死因子-α和白细胞介素-6）以及基质金属蛋白酶3、9和13和金属蛋白酶组织抑制剂-1的表达。组织学和X射线检查显示，与对照组或假手术+尼古丁组相比，骨关节炎组出现软骨退化（组织学对照组vs骨关节炎：p = 0.002，X射线对照组vs骨关节炎：p = 0.004）。尼古丁治疗减少了软骨退变，但无显著差异。与对照组相比，骨关节炎诱导导致促炎细胞因子和基质金属蛋白酶的表达更高。尼古丁给药后，这种作用减弱。促炎细胞因子和基质金属蛋白酶的差异没有达到统计学意义。在目前的小规模研究中，由于保守的统计分析和连续缺乏显著差异，我们无法证明烟碱乙酰胆碱受体刺激对骨关节炎的积极作用。然而，我们发现了相关参数的有希望的趋势，这可能会促使进一步的实验设计，以评估刺激该受体系统作为骨关节炎的额外治疗方法的效力。
Despite the rising number of patients with osteoarthritis, no sufficient chondroprotective and prophylactic therapy for osteoarthritis has been established yet. The purpose of this study was to verify whether stimulation of the nicotinic acetylcholine receptor via nicotine has a beneficial effect on cartilage degeneration in the development of osteoarthritis and is capable of reducing the expression of proinflammatory cytokines and cartilage degrading enzymes in synovial membranes after osteoarthritis induction. Experimental osteoarthritis was induced in Lewis rats using a standardized osteoarthritis model with monoiodoacetate. A total of 16 Lewis rats were randomized into four groups: control, sham + nicotine application, osteoarthritis, and osteoarthritis + nicotine application. Nicotine (0.625 mg/kg twice daily) was administered intraperitoneally for 42 days. We analyzed histological sections, radiological images and the expression of the proinflammatory cytokines, such as interleukin-1β, tumor necrosis factor-α and interleukin-6, and of matrix metalloproteases 3, 9 and 13 and tissue inhibitors of metalloprotease-1 in synovial membranes via quantitative polymerase chain reaction. Histological and x-ray examination revealed cartilage degeneration in the osteoarthritis group compared to control or sham + nicotine groups (histological control vs osteoarthritis: p = 0.002 and x-ray control vs osteoarthritis: p = 0.004). Nicotine treatment reduced the cartilage degeneration without significant differences. Osteoarthritis induction led to a higher expression of proinflammatory cytokines and matrix metalloproteases as compared to control groups. This effect was attenuated after nicotine administration. The differences of proinflammatory cytokines and matrix metalloproteases did not reach statistical significance. With the present small-scale study, we could not prove a positive effect of nicotinic acetylcholine receptor stimulation on osteoarthritis due to a conservative statistical analysis and the consecutive lack of significant differences. Nevertheless, we found promising tendencies of relevant parameters that might prompt further experiments designed to evaluate the potency of stimulation of this receptor system as an additional treatment approach for osteoarthritis.