Byron Christopher R, Trahan Richard A
Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, Unites States.
Front Vet Sci. 2017 Sep 20;4:152. doi: 10.3389/fvets.2017.00152. eCollection 2017.
Osteoarthritis (OA) is a ubiquitous disease affecting many horses. The disease causes chronic pain and decreased performance for patients and great cost to owners for diagnosis and treatment. The most common treatments include systemic non-steroidal anti-inflammatory drugs and intra-articular injection of corticosteroids. There is excellent support for the palliative pain relief these treatments provide; however, they do not arrest progression and may in some instances hasten advancement of disease. Orthobiologic treatments have been investigated as potential OA treatments that may not only ameliorate pain but also prevent or reverse pathologic articular tissue changes. Clinical protocols for intra-articular use of such treatments have not been optimized; the high cost of research and concerns over humane use of research animals may be preventing discovery. The objective of this study was to evaluate a novel articular coculture system for future use in OA treatment research. Concentrations and fold increases in various markers of inflammation (prostaglandin E and tumor necrosis factor-alpha), degradative enzyme activity [matrix metalloproteinase-13 (MMP-13)], cartilage and bone metabolism (bone alkaline phosphatase and dimethyl-methylene blue), and cell death (lactate dehydrogenase) were compared between IL-1-stimulated equine articular cartilage explant cultures and cocultures comprised of osteochondral and synovial explants (OCS). Results suggested that there are differences in responses of culture systems to inflammatory stimulation. In particular, the IL-1-induced fold changes in MMP-13 concentration were significantly different between OCS and cartilage explant culture systems after 96 h. These differences may be relevant to responses of joints to inflammation and could be important to the biological relevance of research findings.
骨关节炎（OA）是一种普遍存在的疾病，影响着许多马匹。这种疾病给患病马匹带来慢性疼痛并导致其运动能力下降，同时给马主带来巨大的诊断和治疗成本。最常见的治疗方法包括全身性非甾体抗炎药和关节内注射皮质类固醇。这些治疗方法在缓解疼痛方面有很好的效果；然而，它们并不能阻止疾病的进展，在某些情况下甚至可能加速疾病的发展。生物治疗已被研究作为潜在的骨关节炎治疗方法，其不仅可以缓解疼痛，还可能预防或逆转关节病理组织变化。此类治疗方法关节内使用的临床方案尚未优化；研究成本高昂以及对实验动物人道使用的担忧可能阻碍了相关发现。本研究的目的是评估一种新型关节共培养系统，以便未来用于骨关节炎治疗研究。比较了白细胞介素 -1 刺激的马关节软骨外植体培养物与由骨软骨和滑膜外植体（OCS）组成的共培养物之间各种炎症标志物（前列腺素 E 和肿瘤坏死因子 -α）、降解酶活性[基质金属蛋白酶 -13（MMP -13）]、软骨和骨代谢（骨碱性磷酸酶和二甲基亚甲基蓝）以及细胞死亡（乳酸脱氢酶）的浓度和增加倍数。结果表明，培养系统对炎症刺激的反应存在差异。特别是，96 小时后，OCS 和软骨外植体培养系统中白细胞介素 -1 诱导的 MMP -13 浓度倍数变化存在显著差异。这些差异可能与关节对炎症的反应有关，并且对研究结果的生物学相关性可能很重要。
