Runx1 Activities in Superficial Zone Chondrocytes, Osteoarthritic Chondrocyte Clones and Response to Mechanical Loading.
Runx1 Activities in Superficial Zone Chondrocytes, Osteoarthritic Chondrocyte Clones and Response to Mechanical Loading.
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DOI：
10.1002/jcp.24727
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发表时间：
2015-02
影响因子：
5.6
通讯作者：
Fanning, Paul J.
中科院分区：
文献类型：
--
作者：
Leblanc, Kimberly T.;Walcott, Marie E.;Gaur, Tripti;O'Connell, Shannon L.;Basil, Kirti;Tadiri, Christina P.;Mason-Savas, April;Silva, Jason A.;van Wijnen, Andre J.;Stein, Janet L.;Stein, Gary S.;Ayers, David C.;Lian, Jane B.;Fanning, Paul J.
Runx 1，造血谱系决定转录因子，存在于软骨膜和软骨细胞中。在这里，我们解决了Runx 1的功能，通过检查在小鼠和人类骨关节炎（OA）的进展和响应机械负荷的软骨中的表达。OA患者和内侧半月板手术失稳小鼠膝关节的滑膜和病变区室检查Runx 1 mRNA（Q-PCR）和蛋白质（免疫印迹，免疫组织化学）表达的变化。Runx 1水平定量响应牛关节软骨的静态机械压缩。Runx 1功能通过细胞增殖（Ki 67、PCNA）和细胞类型表型标志物来评估。Runx 1在正常牛、小鼠和人组织的浅区（SZ）软骨细胞中富集。在牛软骨中增加负荷条件揭示了与Runx 1显著升高的正相关性。Runx 1在小鼠OA病变的外周和人OA软骨细胞“克隆”中高度表达，其中Runx 1与间充质干细胞（MSC）标记物Vcam 1和软骨软骨保护蛋白润滑素（Prg 4）共定位。这些OA诱导的细胞代表增殖细胞群，MPC中的Runx 1缺失降低细胞生长，支持Runx 1对细胞扩增的贡献。正常软骨SZC中Runx 1水平最高表明支持关节软骨细胞独特表型的功能，这反映在压缩条件下上调。我们提出Runx 1与Vcam 1和润滑素在小鼠细胞簇和人OA软骨“克隆”中共表达，参与代偿性合成代谢功能的合作机制。
Runx1, the hematopoietic lineage determining transcription factor, is present in perichondrium and chondrocytes. Here we addressed Runx1 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 were examined for changes in expression of Runx1 mRNA (Q-PCR) and protein (immunoblot, immunohistochemistry). Runx1 levels were quantified in response to static mechanical compression of bovine articular cartilage. Runx1 function was assessed by cell proliferation (Ki67, PCNA) and cell type phenotypic markers. Runx1 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 Runx1. Runx1 becomes highly expressed at the periphery of mouse OA lesions and in human OA chondrocyte ‘clones’ where Runx1 co-localizes with Vcam1, the mesenchymal stem cell (MSC) marker and lubricin (Prg4), a cartilage chondroprotective protein. These OA induced cells represent a proliferative cell population, Runx1 depletion in MPCs decreases cell growth, supporting Runx1 contribution to cell expansion. The highest Runx1 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 Runx1 co-expression with Vcam1 and lubricin in murine cell clusters and human ‘clones’ of OA cartilage, participate in a cooperative mechanism for a compensatory anabolic function.
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影响因子：
--
作者：
Jay, Gregory D.;Fleming, Braden C.;Watkins, Bryn A.;McHugh, Karen A.;Anderson, Scott C.;Zhang, Ling X.;Teeple, Erin;Waller, Kimberly A.;Elsaid, Khaled A.
通讯作者：
Elsaid, Khaled A.
影响因子：
--
作者：
Lotz, Martin K.;Otsuki, Shuhei;Grogan, Shawn P.;Sah, Robert;Terkeltaub, Robert;D'Lima, Darryl
通讯作者：
D'Lima, Darryl
影响因子：
4
作者：
Komori, T
通讯作者：
Komori, T
影响因子：
3.6
作者：
Hidaka, C;Cheng, C;Torzilli, PA
通讯作者：
Torzilli, PA
影响因子：
4
作者：
Markova, Elena N.;Kantidze, Omar L.;Razin, Sergey V.
通讯作者：
Razin, Sergey V.