Clements Dylan N, Carter Stuart D, Innes John F, Ollier William E R, Day Philip J R
The Musculoskeletal Research Group, c/o Department of Veterinary Pathology, Faculty of Veterinary Science, University of Liverpool, Liverpool, L69 3BX, UK.
Arthritis Res Ther. 2006;8(6):R158. doi: 10.1186/ar2053.
The molecular basis to mammalian osteoarthritis (OA) is unknown. We hypothesised that the expression of selected proteases, matrix molecules, and collagens believed to have a role in the pathogenesis of OA would be changed in naturally occurring canine OA cartilage when compared to normal articular cartilage. Quantitative (real-time) reverse transcriptase-polymerase chain reaction assays were designed measuring the expression of selected matrix molecules (collagens and small leucine-rich proteoglycans), key mediators of the proteolytic degradation of articular cartilage (metalloproteinases, cathepsins), and their inhibitors (tissue inhibitors of matrix metalloproteinases). All data were normalised using a geometric mean of three housekeeping genes, and the results subjected to power calculations and corrections for multiple hypothesis testing. We detected increases in the expression of BGN, COL1A2, COL2A1, COL3A1, COL5A1, CSPG2, CTSB, CTSD, LUM, MMP13, TIMP1, and TNC in naturally occurring canine OA. The expression of TIMP2 and TIMP4 was significantly reduced in canine OA cartilage. The patterns of gene expression change observed in naturally occurring canine OA were similar to those reported in naturally occurring human OA and experimental canine OA. We conclude that the expression profiles of matrix-associated molecules in end-stage mammalian OA may be comparable but that the precise aetiologies of OA affecting specific joints in different species are presently unknown.
哺乳动物骨关节炎(OA)的分子基础尚不清楚。我们推测,与正常关节软骨相比,在自然发生的犬类OA软骨中,一些被认为在OA发病机制中起作用的蛋白酶、基质分子和胶原蛋白的表达会发生变化。设计了定量(实时)逆转录-聚合酶链反应分析,以测量选定的基质分子(胶原蛋白和富含亮氨酸的小分子蛋白聚糖)、关节软骨蛋白水解降解的关键介质(金属蛋白酶、组织蛋白酶)及其抑制剂(基质金属蛋白酶组织抑制剂)的表达。所有数据均使用三个管家基因的几何平均值进行归一化,并对结果进行功效计算和多重假设检验校正。我们检测到在自然发生的犬类OA中,BGN、COL1A2、COL2A1、COL3A1、COL5A1、CSPG2、CTSB、CTSD、LUM、MMP13、TIMP1和TNC的表达增加。犬类OA软骨中TIMP2和TIMP4的表达显著降低。在自然发生的犬类OA中观察到的基因表达变化模式与自然发生的人类OA和实验性犬类OA中报道的模式相似。我们得出结论,终末期哺乳动物OA中基质相关分子的表达谱可能具有可比性,但目前尚不清楚影响不同物种特定关节的OA的确切病因。