Steck Eric, Breit Stephen, Breusch Steffen J, Axt Matthias, Richter Wiltrud
Department of Orthopaedic Surgery, University of Heidelberg, Schlierbacher Landstrasse 200a, 69118, Heidelberg, Germany.
Biochem Biophys Res Commun. 2002 Nov 22;299(1):109-15. doi: 10.1016/s0006-291x(02)02585-8.
The knowledge of molecular alterations in osteoarthritic cartilage is important to identify novel therapeutic targets or to develop new diagnostic tools. We aimed to characterize the molecular response to cartilage degeneration by identification of differentially expressed genes in human osteoarthritic versus normal cartilage. Gene fragments selectively amplified in osteoarthritic cartilage by cDNA representational difference analysis included YKL-39 and the oesophageal-cancer-related-gene-4 (ECRG4). YKL-39 expression was significantly upregulated in cartilage from patients with osteoarthritis (n=14) versus normal subjects (n=8) according to real-time PCR (19-fold, p=0.009) and cDNA array analysis (mean 15-fold, p<0.001) and correlated with collagen 2 up-regulation. In contrast, the homologous cousin molecule YKL-40 (chitinase 3-like 1), which is elevated in serum and synovial fluid of patients with arthritis, showed no significant regulation in OA cartilage. Enhanced levels of YKL-40 may, therefore, be derived from synovial cells while modulation of YKL-39 and collagen 2 expression reflected the cartilage metabolism in response to degradation.
了解骨关节炎软骨中的分子改变对于确定新的治疗靶点或开发新的诊断工具至关重要。我们旨在通过鉴定人类骨关节炎软骨与正常软骨中差异表达的基因，来表征对软骨退变的分子反应。通过cDNA代表性差异分析在骨关节炎软骨中选择性扩增的基因片段包括YKL-39和食管癌相关基因4（ECRG4）。根据实时PCR（19倍，p = 0.009）和cDNA阵列分析（平均15倍，p <0.001），骨关节炎患者（n = 14）的软骨中YKL-39表达相对于正常受试者（n = 8）显著上调，并且与胶原蛋白2上调相关。相比之下，在关节炎患者的血清和滑液中升高的同源分子YKL-40（几丁质酶3样1）在骨关节炎软骨中未显示出显著调节。因此，YKL-40水平的升高可能源自滑膜细胞，而YKL-39和胶原蛋白2表达的调节反映了软骨对退变的代谢反应。
