Osteoarthritic Synovial Tissue Inhibition of Proteoglycan Production in Human Osteoarthritic Knee Cartilage Establishment and Characterization of a Long-Term Cartilage Synovium-Coculture
Osteoarthritic Synovial Tissue Inhibition of Proteoglycan Production in Human Osteoarthritic Knee Cartilage Establishment and Characterization of a Long-Term Cartilage Synovium-Coculture
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DOI：
10.1002/art.30364
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发表时间：
2011-07-01
影响因子：
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通讯作者：
van Osch, Gerjo J. V. M.
中科院分区：
文献类型：
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作者：
Beekhuizen, Michiel;Bastiaansen-Jenniskens, Yvonne M.;van Osch, Gerjo J. V. M.
目标。尽管软骨和滑膜在骨关节炎(OA)中都受到影响，但目前还没有人骨关节炎组织的体外共培养模型。本研究的目的是建立一种包括膝关节OA患者滑膜和软骨的体外模型。将人膝关节骨性关节炎软骨和滑膜分别单独或共培养21d。通过组织学评价和分析乳酸脱氢酶(LDH)释放、基质金属蛋白酶(MMP)活性、糖胺聚糖(GAG)的含量、释放和合成以及细胞因子的产生来评价滑膜组织的功能及其对软骨代谢的影响。为了评估干预模型系统的可能性，研究了曲安奈德的作用。在整个培养过程中，骨性关节炎滑膜组织仍然存活并产生细胞因子。滑膜和软骨外植体的单一培养产生不同的细胞因子亚群，在共培养中发现的亚群与先前在OA滑液中描述的亚群最相似。只有滑膜外植体单独培养和共培养中才能检测到基质金属蛋白酶活性。混合培养显示最终的GAG含量减少(P<；0.001)，这是由于抑制了GAG的产生(P<；0.02)，而不是增加了GAG的释放。加入曲安奈德可抑制共培养和滑膜组织单培养中细胞因子的产生和基质金属蛋白酶的活性，并拮抗共培养对GAG产生的抑制。然而，在软骨单一培养中，曲安奈德减少了GAG的产生。OA滑膜通过减少GAG的产生而影响软骨代谢。曲安奈德可以减轻滑膜组织的这种影响，但当加入到软骨单一培养中时会受到抑制。这些结果清楚地表明，组织共培养作为研究骨性关节炎病理生理学和开发可能的干预措施的一种有前途的工具是重要的。
Objective. Although both cartilage and synovium are affected in osteoarthritis (OA), no in vitro coculture models of human OA tissue have been described. The aim of this study was to develop an in vitro model that includes both the synovium and cartilage of patients with knee OA.Methods. Explants of human OA cartilage and synovium were cultured alone or in coculture for 21 days. Histologic evaluation and analyses of lactate dehydrogenase release, matrix metalloproteinase (MMP) activity, content, release, and synthesis of glycosaminoglycan (GAG), and cytokine production were used to evaluate synovial tissue functionality and its effect on cartilage metabolism. To assess the possibility of intervention in the model system, the effect of triamcinolone was studied.Results. Throughout the entire culture period, OA synovial tissue remained viable and produced cytokines. Monocultures of synovial and cartilage explants produced different cytokine subsets, with the subsets found in coculture being most similar to those previously described in OA synovial fluid. MMP activity was detectable only in the synovial explant monoculture and in coculture. Cocultures showed a reduction in final GAG content (P < 0.02), attributable to an inhibition of GAG production (P < 0.001) rather than an increase in GAG release. Addition of triamcinolone inhibited cytokine production and MMP activity in coculture and synovial tissue monoculture and counteracted the inhibition of GAG production induced by coculture. In cartilage monoculture, however, triamcinolone reduced GAG production.Conclusion. OA synovium affects cartilage metabolism by reducting GAG production. Triamcinolone can relieve this effect of synovial tissue, while being inhibitory when added to cartilage monoculture. These results clearly indicate the importance of tissue coculture as a promising tool for studying OA pathophysiology and for development of possible interventions.