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美洛昔康对自然发生骨关节炎犬关节软骨细胞代谢的体外作用。

In vitro effects of meloxicam on metabolism in articular chondrocytes from dogs with naturally occurring osteoarthritis.

作者信息

Budsberg Steven C, Stoker Aaron M, Johnston Spencer A, Liska William, Reno Lisa R, Cook James L

机构信息

Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.

出版信息

Am J Vet Res. 2013 Sep;74(9):1198-205. doi: 10.2460/ajvr.74.9.1198.

Abstract

OBJECTIVE

To assess effects of in vitro meloxicam exposure on metabolism in articular chondrocytes from dogs with naturally occurring osteoarthritis.

SAMPLE

Femoral head cartilage from 16 dogs undergoing total hip replacement.

PROCEDURES

Articular cartilage samples were obtained. Tissue sulfated glycosaminoglycan (SGAG), collagen, and DNA concentrations were measured. Collagen, SGAG, chondroitin sulfate 846, NO, prostaglandin E2 (PGE2), and matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, and MMP-13 concentrations in culture medium were analyzed. Aggrecan, collagen II, MMP-2, MMP-3, MMP-9, MMP-13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4, ADAMTS-5, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, TIMP-3, interleukin-1β, tumor necrosis factor-α, cyclooxygenase-1, cyclooxygenase-2, and inducible nitric oxide synthase gene expression were evaluated. Comparisons between tissues cultured without (control) and with meloxicam at concentrations of 0.3, 3.0, and 30.0 μg/mL for up to 30 days were performed by means of repeated-measures analysis.

RESULTS

Meloxicam had no effect on chondrocyte SGAG, collagen, or DNA concentrations. Expression of ADAMTS-5 was significantly decreased in all groups on all days, compared with the day 0 value. On day 3, culture medium PGE2 concentrations were significantly lower in all meloxicam-treated groups, compared with values for controls, and values remained low. Culture medium MMP-3 concentrations were significantly lower on day 30 than on day 3 in all meloxicam-treated groups.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that in vitro meloxicam treatment of osteoarthritic canine cartilage for up to 30 days did not induce matrix degradation or stimulate MMP production. Meloxicam lowered PGE2 release from this tissue, and effects on tissue chondrocyte content and matrix composition were neutral.

摘要

目的

评估体外给予美洛昔康对自然发生骨关节炎犬关节软骨细胞代谢的影响。

样本

16只接受全髋关节置换术的犬的股骨头软骨。

方法

获取关节软骨样本。测量组织硫酸化糖胺聚糖(SGAG)、胶原蛋白和DNA浓度。分析培养基中胶原蛋白、SGAG、硫酸软骨素846、一氧化氮(NO)、前列腺素E2(PGE2)以及基质金属蛋白酶(MMP)-2、MMP-3、MMP-9和MMP-13的浓度。评估聚集蛋白聚糖、胶原蛋白II、MMP-2、MMP-3、MMP-9、MMP-13、含血小板反应蛋白基序的解聚素样金属蛋白酶(ADAMTS)-4、ADAMTS-5、金属蛋白酶组织抑制剂(TIMP)-1、TIMP-2、TIMP-3、白细胞介素-1β、肿瘤坏死因子-α、环氧化酶-1、环氧化酶-2和诱导型一氧化氮合酶基因的表达。通过重复测量分析对未添加美洛昔康(对照)以及添加浓度为0.3、3.0和30.0μg/mL美洛昔康培养长达30天的组织进行比较。

结果

美洛昔康对软骨细胞的SGAG、胶原蛋白或DNA浓度没有影响。与第0天的值相比,所有组在所有天数ADAMTS-5的表达均显著降低。在第3天,所有美洛昔康处理组培养基中的PGE2浓度与对照组相比显著降低,且该值持续较低。在第30天,所有美洛昔康处理组培养基中的MMP-3浓度显著低于第3天。

结论及临床意义

结果表明,体外给予美洛昔康处理骨关节炎犬软骨长达30天不会诱导基质降解或刺激MMP产生。美洛昔康降低了该组织中PGE2的释放,并且对组织软骨细胞含量和基质组成的影响是中性的。

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