Chondroitin sulfate sulfation motifs as putative biomarkers for isolation of articular cartilage progenitor cells
Chondroitin sulfate sulfation motifs as putative biomarkers for isolation of articular cartilage progenitor cells
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DOI：
10.1369/jhc.7a7320.2007
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发表时间：
2008-02-01
影响因子：
3.2
通讯作者：
Hughes, Clare E.
中科院分区：
文献类型：
--
作者：
Hayes, Anthony J.;Tudor, Debbie;Hughes, Clare E.
骨关节炎是一种慢性、使人衰弱的关节疾病，其特征是关节软骨进行性破坏。最近，许多研究在关节软骨内发现了一种软骨祖细胞群，其具有显著的修复/再生潜力。到目前为止，这些细胞几乎没有可靠的生物标志物。在这项研究中，我们表明识别蛋白聚糖上糖胺聚糖中新型硫酸软骨素硫酸化基序表位的单克隆抗体可用于特异性识别组织浅表层内代谢不同的细胞亚群，并且流式细胞术分析能够识别这些细胞亚群。荧光色素共定位分析表明，硫酸软骨素硫酸化基序与干细胞微环境内的一系列细胞和细胞外基质蛋白聚糖相关，包括基底膜聚糖和聚集蛋白聚糖，但不包括多功能蛋白聚糖。这些硫酸化基序在浅表层软骨细胞微环境内的独特分布似乎表明了干/祖细胞分化的早期阶段，并且与这些分子在调节软骨形成方面发挥功能作用是一致的。这些细胞的分离和进一步表征将有助于更好地理解新型硫酸软骨素硫酸化在关节软骨发育中的作用，并可能对关节软骨修复领域有重大贡献。
Osteoarthritis is a chronic, debilitating joint disease characterized by progressive destruction of articular cartilage. Recently, a number of studies have identified a chondroprogenitor cell population within articular cartilage with significant potential for repair/regeneration. As yet, there are few robust biomarkers of these cells. In this study, we show that monoclonal antibodies recognizing novel chondroitin sulfate sulfation motif epitopes in glycosaminoglycans on proteoglycans can be used to identify metabolically distinct subpopulations of cells specifically within the superficial zone of the tissue and that flow cytometric analysis can recognize these cell subpopulations. Fluorochrome colocalization analysis suggests that the chondroitin sulfate sulphation motifs are associated with a range of cell and extracellular matrix proteoglycans within the stem cell niche that include perlecan and aggrecan but not versican. The unique distributions of these sulphation motifs within the microenvironment of superficial zone chondrocytes, seems to designate early stages of stem/progenitor cell differentiation and is consistent with these molecules playing a functional role in regulating aspects of chondrogenesis. The isolation and further characterization of these cells will lead to an improved understanding of the role novel chondroitin sulfate sulfation plays in articular cartilage development and may contribute significantly to the field of articular cartilage repair.