Analysis of heat shock proteins and cytokines expressed during early stages of osteoarthritis in a mouse model.

Analysis of heat shock proteins and cytokines expressed during early stages of osteoarthritis in a mouse model.
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DOI:
10.1016/s1063-4584(97)80036-2
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发表时间:
1997-09
影响因子:
7
通讯作者:
K. Takahashi;T. Kubo;R. Goomer;D. Amiel;K. Kobayashi;J. Imanishi;R. Teshima;Y. Hirasawa
K. Takahashi;T. Kubo;R. Goomer;D. Amiel;K. Kobayashi;J. Imanishi;R. Teshima;Y. Hirasawa
中科院分区:
医学2区
文献类型:
--
作者:
K. Takahashi;T. Kubo;R. Goomer;D. Amiel;K. Kobayashi;J. Imanishi;R. Teshima;Y. Hirasawa

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目的:骨关节炎(OA)是一种使关节衰弱的疾病。受影响个体的关节的特征在于关节软骨的进行性退化,导致炎症和疼痛。热休克蛋白(HSPs)的表达是所有细胞在应激下普遍存在的自我保护机制,并且骨关节炎个体的滑膜含有高水平的细胞因子。本研究旨在确定热休克蛋白和细胞因子在OA中的作用。方法:我们已经研究了在OA的早期阶段,在小鼠(C57黑小鼠),已知开发自发性OA病变的关节软骨中的热休克蛋白和细胞因子的存在。以近亲小鼠(C57 BL/6)的关节软骨作为对照。采用逆转录-聚合酶链反应(RT-PCR)检测HSP 32、HSP 47、HSP 60、HSP 70、HSP 84、HSP 86和细胞因子IL-1 β、IL-6、TNF-α、IFN-γ的mRNA表达。结果:C57黑鼠软骨中HSP 47、HSP 70、HSP 86、IL-6和IFN-γ的mRNA水平上调,而HSP 32、HSP 60、HSP 84和IL-1β的表达水平无变化。IL-1β、IL-6、TNF-α和IFN-γ mRNA的表达分别与HSP 60、HSP 47、HSP 70和HSP 70/HSP 86 mRNA的表达相关。结论:本研究结果提示,软骨细胞在OA早期处于非生理性应激状态。另外,在C57黑小鼠中,HSP 70与两种不同的高表达细胞因子相关,提示HSP 70可能是OA早期的特征性指标。
Summary OBJECTIVE:: Osteoarthritis (OA) is a debilitating disease of the joints. The joints of affected individuals are characterized by a progressive degeneration of articular cartilage leading to inflammation and pain. The expression of heat shock proteins (HSPs) is a ubiquitous self-protective mechanism of all cells under stress, furthermore, the synovium of osteoarthritic individuals contains high levels of cytokines. This study seeks to establish the role of HSPs and cytokines in OA. METHODS:: We have investigated the presence of HSPs and cytokines in articular cartilage during early stages of OA in a mouse that is known to develop spontaneous OA lesions (C57 black mouse). The articular cartilage from closely related mice (C57BL/6) was used as control. Messenger RNAs (mRNAs) for HSPs (HSP32, HSP47, HSP60, HSP70, HSP84 and HSP86) and cytokines [interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)] were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:: The mRNA levels of HSP47, HSP70, HSP86, IL-6, and IFN-γ were up-regulated in the cartilage of C57 black mice, whereas, the level of expression of HSP32, HSP60, HSP84 and IL-1β remained unchanged. Furthermore, the expression of IL-1β, IL-6, TNF-α and IFN-γ mRNA was associated with expression of HSP60, HSP47, HSP70 and HSP70/HSP86 mRNA, respectively. CONCLUSIONS:: The findings in this study suggest that chondrocytes are conditioned under non-physiological stress during early stages of OA, In addition, among HSPs, HSP70 was associated with two different highly expressed cytokines in C57 black mice, indicating the possible role of HSP70 as a characteristic indicator of early stage of OA.