Runxi Activities in Superficial Zone Chondrocytes Osteoarthritic Chondrocyte Clones and Response to Mechanical Loading

KIHBERLY T. LEBLANC; MARIE E. WALCOTT; TRIPTI GAURSHANNON L

摘要

Runx I, the hematopoietic lineage determining transcription factor, is present in perichondrium and chondrocytes. Here we addressedRunxl functions, by examining expression in cartilage during mouse and human osteoarthritis (OA) progression and in response to mechanical loading. Spared and diseased compartments in knees of OA patients and in mice with surgical destabilization of the medial meniscus ￥/ere examined for changes in expression of Runxf mRNA (Q-PCR) and protein (immunobiot, immunohistochemistry), Runxl levels were quantified in response to static mechanical compression of bovine articular cartilage. Runxl function was assessed by ceil proliferation (Ki67, PCNA) and ceii type phenotypic markers. Runxl is enriched in superficial zone (SZ) chondrocytes of normal bovine, mouse, and human tissues. Increasing loading conditions in bovine cartilage revealed a positive correlation with a significant elevation of Rurtx I. Runx 1 becomes highly expressed at the periphery of mouse OA lesions and in human OA chondrocyte 'clones' where Runx 1 co-localizes with Vcarrs i, the mesenchymal stem cell (MSC) marker and lubricin (Prg4), a cartilage chondroprotective protein, These OA induced cells represent a proliferative cell population, Runxl depletion in MFCs decreases cell growth, supporting Runxl contribution to cell expansion. The highest Runxl levels in SZC of normal cartilage suggest a function that supports the unique phenotype of articular chondrocytes, reflected by upregulation under conditions of compression. We propose Runxl co-expression with Vcam I and lubricin in murine cell dusters and human 'clones* of OA cartilage, participate in a cooperative mechanism for a compensatory anabolic function.

机译：Runx我造血血统决定转录因子,存在于软骨膜和软骨细胞。功能,通过检查表达式在软骨在老鼠和人类骨关节炎(OA)进展和对机械的回应装载。双膝OA患者和外科在老鼠身上不稳定的内侧半月板￥/之前检查Runxf mRNA的表达的变化(Q-PCR)和蛋白质(immunobiot,免疫组织化学),Runxl水平量化在静态机械压缩的牛关节软骨。函数被装天花板扩散评估(PCNA Ki67)和ceii类型表型标记。Runxl是在表面富集带(深圳)软骨细胞正常的牛、小鼠和人类组织。软骨的正相关重要的海拔Rurtx i Runx 1外围的高度表示鼠标OA在人类OA软骨细胞损伤和“克隆”Runx 1硝唑Vcarrs我,间充质干细胞(MSC)和lubricin标志(Prg4)软骨chondroprotective蛋白质,这些OA诱导细胞增殖细胞群,Runxl mfc电池损耗减少细胞生长,支持Runxl对细胞扩张的贡献。水平SZC正常软骨的建议函数支持独特的表型关节软骨细胞,用upregulation才能体现条件下的压缩。co-expression Vcam我和lubricin鼠* OA软骨细胞抹布和人类的克隆,参与的合作机制补充合成代谢功能。

Runxi Activities in Superficial Zone Chondrocytes Osteoarthritic Chondrocyte Clones and Response to Mechanical Loading

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