Salminen-Mankonen H, Säämänen A-M, Jalkanen M, Vuorio E, Pirilä L
Department of Medical Biochemistry, University of Turku, Finland.
Scand J Rheumatol. 2005 Nov-Dec;34(6):469-74. doi: 10.1080/03009740500304338.
Mice heterozygous for the Del1 transgene locus with a short deletion mutation in the type II collagen gene develop early-onset degenerative changes in the knee joints that progress to end-stage osteoarthritis by the age of 12-15 months. This study focuses on the expression and distribution of syndecan-1, a cell-surface heparan sulfate proteoglycan, during the development of osteoarthritic cartilage degeneration, to better understand its role in this disease.
Northern analyses of total RNA extracted from knee joints of transgenic Del1 mice and their nontransgenic controls were used to monitor changes in syndecan-1 mRNA levels during development, growth, ageing, and cartilage degeneration. Immunohistochemistry was used to study the distribution of syndecan-1 in the knee joints at different stages of cartilage degeneration.
Syndecan-1 mRNA was present in knee joints throughout life, with the highest mRNA levels in ageing knee joints. In Del1 mice, a transient upregulation of syndecan-1 mRNA synthesis was observed at the age of 6 months coinciding with early stages of cartilage degeneration and a period of attempted repair. Immunostaining for syndecan-1 was most intense in chondrocytes of superficial and intermediate zones of articular cartilage adjacent to defect areas. Chondrocyte clusters also stained strongly for syndecan-1.
The present temporospatial expression data on upregulation of syndecan-1 in articular cartilage during early stages of cartilage degeneration suggest that this molecule is involved in the attempted repair of cartilage fibrillations. Combined with the known role of syndecan-1 during skeletal development and wound healing, this interesting finding warrants further validation.
携带Del1转基因位点且Ⅱ型胶原基因存在短缺失突变的杂合子小鼠，其膝关节会出现早发性退行性改变，并在12至15个月大时发展为终末期骨关节炎。本研究聚焦于细胞表面硫酸乙酰肝素蛋白聚糖syndecan-1在骨关节炎软骨退变发展过程中的表达和分布，以更好地理解其在该疾病中的作用。
对从转基因Del1小鼠及其非转基因对照的膝关节中提取的总RNA进行Northern分析，以监测syndecan-1 mRNA水平在发育、生长、衰老和软骨退变过程中的变化。采用免疫组织化学方法研究syndecan-1在软骨退变不同阶段膝关节中的分布。
syndecan-1 mRNA在整个生命过程中都存在于膝关节中，在衰老的膝关节中mRNA水平最高。在Del1小鼠中，6个月大时观察到syndecan-1 mRNA合成的短暂上调，这与软骨退变的早期阶段以及一段尝试修复的时期相吻合。syndecan-1的免疫染色在与缺损区域相邻的关节软骨表层和中层区域的软骨细胞中最为强烈。软骨细胞簇对syndecan-1的染色也很强。
目前关于软骨退变早期关节软骨中syndecan-1上调的时空表达数据表明，该分子参与了软骨纤维化的尝试性修复。结合syndecan-1在骨骼发育和伤口愈合中的已知作用，这一有趣的发现值得进一步验证。
