Muscle cells enhance resistance to pro-inflammatory cytokine-induced cartilage destruction.
Muscle cells enhance resistance to pro-inflammatory cytokine-induced cartilage destruction.
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DOI：
10.1016/j.bbrc.2009.12.138
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发表时间：
2010-01-29
影响因子：
3.1
通讯作者：
Zeng, Li
中科院分区：
文献类型：
--
作者：
Cairns, Dana M.;Uchimura, Tomoya;Kwon, Heenam;Lee, Philip G.;Seufert, Christopher R.;Matzkin, Elizabeth;Zeng, Li
促炎细胞因子IL-1、β和肿瘤坏死因子α通过破坏软骨细胞的合成代谢和分解代谢活性，在关节炎的表现中发挥重要作用。我们观察到了一种新的软骨调节机制，肌肉细胞通过这种机制降低了软骨细胞对IL-1β和肿瘤坏死因子α的反应。我们发现，与肌肉细胞共培养或在肌肉细胞条件培养液中培养的软骨细胞显著增强软骨基质蛋白(II型胶原和IX型胶原)的表达，并对抗IL-1β和肿瘤坏死因子α诱导的软骨损伤。我们的结果表明，这种作用是通过抑制促炎症细胞因子信号通路的关键成分(包括NFκB、ESE-1、COX-2和GADD45β)的表达，导致软骨降解酶(MMPs和ADAMTS4)的表达减弱而实现的。因此，我们的工作揭示了肌肉在调节软骨内稳态和对促炎刺激的反应中的潜在作用，并为设计关节退行性疾病(如关节炎)的治疗策略提供了见解。
Pro-inflammatory cytokines IL-1β and TNFα play important roles in the manifestation of arthritis by disrupting the anabolic and catabolic activities of the chondrocytes. We observed a novel mechanism of cartilage regulation by which muscle cells diminish the response of chondrocytes to IL-1β and TNFα. We found that chondrocytes cocultured with muscle cells or cultured in muscle cell-conditioned medium significantly enhanced the expression of cartilage matrix proteins (collagen II and collagen IX) and resisted IL-1β and TNFα-induced cartilage damage. Our data suggest that this effect is achieved by inhibiting the expression of key components of the signaling pathways of pro-inflammatory cytokines (including NFκB, ESE-1, Cox-2 and GADD45β), leading to attenuated expression of cartilage degrading enzymes (MMPs and ADAMTS4). Therefore, our work unveils a potential role of muscle in regulating cartilage homeostasis and response to pro-inflammatory stimuli, and provides insights on designing treatment strategies for joint degenerative diseases such as arthritis.
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