College of Veterinary Medicine, Cornell University, NY, USA.
Equine Vet J. 2010 Nov;42(8):693-9. doi: 10.1111/j.2042-3306.2010.00140.x. Epub 2010 Sep 14.
Understanding the expression of catabolic and anabolic genes during osteoarthritis progression should help to identify the major mediators of the disease.
To compare the cytokine and anabolic marker concentrations in synovium, synovial fluid and cartilage between normal and osteoarthritic joints.
Carpi from horses age 2-11 years were used. Tissues were harvested at the time of surgery or euthanasia, and RNA was isolated for RT-PCR analysis. Tumour necrosis factor alpha (TNFα), interleukin-1beta (IL-1β), aggrecanase 1 (ADAMTS-4), aggrecanase 2 (ADAMTS-5), matrix metalloproteinase-13 (MMP-13), interleukin 17 (IL-17) and collagen type I alpha 1(Col-1) expression were determined in synovium. TNFα, IL-1β, ADAMTS-4, ADAMTS-5, MMP-13, IL-17, collagen type IIB (Col-2B), and aggrecan expression were determined in cartilage. TNFα concentration in the synovial fluid was determined by enzyme-linked immunosorbent assay (ELISA).
Expression of TNFα, ADAMTS-5 and MMP-13 was significantly increased in synovial tissue from OA joints. Synovial membrane IL-1β abundance showed only moderate elevations in OA, without reaching significant levels. Cytokine expression was increased significantly in OA cartilage samples, particularly TNFα, IL-1β, ADAMTS-4 and MMP-13; and collagen type I expression was significantly increased in synovial tissues from OA groups. Collagen type II message was diminished in mild and moderate stages of OA, but rebounded to significant elevations in severely degenerate joints. Conversely, aggrecan levels significantly declined in cartilage from all OA groups. Synovial fluid TNFα peptide concentration was significantly increased in severe OA cases.
TNFα was increased in all degrees of equine OA, and was abundantly expressed in synovial membrane and cartilage. IL-1β was overexpressed in OA cartilage, but not to a significant extent in synovium.
Control of TNFα should be considered further as a target in the treatment of OA. ADAMTS-4 may be the primary aggrecanase causing cartilage breakdown in OA.
了解骨关节炎进展过程中分解代谢和合成代谢基因的表达情况，有助于确定该疾病的主要介质。
比较正常关节和骨关节炎关节滑膜、滑液和软骨中的细胞因子和合成代谢标志物浓度。
使用 2-11 岁马的腕骨。在手术或安乐死时采集组织，并分离 RNA 进行 RT-PCR 分析。测定滑膜中肿瘤坏死因子-α (TNFα)、白细胞介素-1β (IL-1β)、聚集蛋白水解酶 1 (ADAMTS-4)、聚集蛋白水解酶 2 (ADAMTS-5)、基质金属蛋白酶-13 (MMP-13)、白细胞介素 17 (IL-17) 和 I 型胶原α 1 (Col-1)的表达。测定软骨中 TNFα、IL-1β、ADAMTS-4、ADAMTS-5、MMP-13、IL-17、IIB 型胶原 (Col-2B) 和聚集蛋白的表达。通过酶联免疫吸附试验 (ELISA) 测定滑液中 TNFα 的浓度。
OA 关节滑膜组织中 TNFα、ADAMTS-5 和 MMP-13 的表达显著增加。OA 滑膜膜 IL-1β 丰度仅中度升高，但未达到显著水平。OA 软骨样本中的细胞因子表达显著增加，尤其是 TNFα、IL-1β、ADAMTS-4 和 MMP-13；OA 组滑膜组织中 I 型胶原表达显著增加。OA 轻中度阶段 II 型胶原表达减少，但在严重退变关节中反弹至显著升高。相反，软骨中聚集蛋白水平显著降低。OA 严重病例滑液中 TNFα 肽浓度显著升高。
在所有程度的马 OA 中，TNFα 均增加，在滑膜膜和软骨中大量表达。OA 软骨中过度表达了 IL-1β，但在滑膜中未达到显著水平。
进一步考虑将 TNFα 作为 OA 治疗的靶点。ADAMTS-4 可能是导致 OA 软骨破坏的主要聚集蛋白水解酶。
