Muscle cell-derived factors inhibit inflammatory stimuli-induced damage in hMSC-derived chondrocytes.
Muscle cell-derived factors inhibit inflammatory stimuli-induced damage in hMSC-derived chondrocytes.
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肌细胞衍生因子抑制 hMSC 衍生软骨细胞中炎症刺激诱导的损伤。
DOI：
10.1016/j.joca.2013.04.011
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发表时间：
2013-07
影响因子：
7
通讯作者：
Zeng, L.
中科院分区：
文献类型：
--
作者：
Rainbow, R. S.;Kwon, H.;Foote, A. T.;Preda, R. C.;Kaplan, D. L.;Zeng, L.
在骨关节炎的发病过程中，促炎细胞因子在诱导软骨降解中起重要作用。肌肉是位于软骨附近的原位组织。然而，肌肉对软骨的非负荷生化作用在很大程度上尚未被探索。在这里，我们测试的假设，肌肉细胞可以调节的反应，促炎性细胞因子介导的损伤软骨细胞来源于人骨髓间充质干细胞（hMSCs）。使hMSC在多孔丝支架中在典型的软骨形成培养基中经历软骨形成分化12天。在接下来的9天中，将细胞在含有50%源自C2 C12肌细胞或成纤维细胞对照细胞的条件培养基的软骨形成培养基中培养，并接受促炎细胞因子IL-1β或TNFα的处理。IL-1β和TNFα均诱导多种MMPs和肥大标志物Runx 2和X型胶原的强烈表达。引人注目的是，在C2 C12肌细胞条件培养基中培养hMSC衍生的软骨细胞强烈抑制所有这些基因的表达，GAG含量和基质蛋白的组织学评价进一步证实了这一结果。为了确定这些影响是否是由于软骨细胞生长和存活的改变，我们检测了细胞增殖标记Ki 67、细胞周期阻滞标记p21和p53以及凋亡标记caspase 3的表达。肌细胞条件培养基促进增殖并抑制凋亡，从而表明可能减少通常伴随软骨炎症的细胞老化和死亡。我们的研究结果表明，在软骨稳态肌肉的作用，并提供深入了解设计策略，促进抗促炎细胞因子在hMSC衍生的软骨细胞。
Pro-inflammatory cytokines play an important role in inducing cartilage degradation during osteoarthritis pathogenesis. Muscle is a tissue that lies near cartilage in situ. However, muscle’s non-loading biochemical effect on cartilage has been largely unexplored. Here, we tested the hypothesis that muscle cells can regulate the response to pro-inflammatory cytokine-mediated damage in chondrocytes derived from human bone marrow-derived mesenchymal stem cells (hMSCs). hMSCs were allowed to undergo chondrogenic differentiation in porous silk scaffolds in the typical chondrogenic medium for 12 days. For the next 9 days, the cells were cultured in chondrogenic medium containing 50% conditioned medium derived from C2C12 muscle cells or fibroblast control cells, and were subject to treatments of pro-inflammatory cytokines IL-1β or TNFα. Both IL-1β and TNFα-induced strong expression of multiple MMPs and hypertrophic markers Runx2 and type X collagen. Strikingly, culturing hMSC-derived chondrocytes in C2C12 muscle cell conditioned medium strongly inhibited the expression of all these genes, a result further confirmed by GAG content and histological evaluation of matrix protein. To determine whether these effects were due to altered chondrocyte growth and survival, we assayed the expression of cell proliferation marker Ki67, cell cycle arrest markers p21 and p53, and apoptosis marker caspase 3. Muscle cell-conditioned medium promoted proliferation and inhibited apoptosis, thereby suggesting a possible decrease in the cellular aging and death that typically accompanies cartilage inflammation. Our findings suggest the role of muscle in cartilage homeostasis and provide insight into designing strategies for promoting resistance to pro-inflammatory cytokines in hMSC-derived chondrocytes.
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影响因子：
3.2
作者：
Elkasrawy, Moataz;Immel, David;Hamrick, Mark W.
通讯作者：
Hamrick, Mark W.
影响因子：
--
作者：
Hootman, JM;Helmick, CG
通讯作者：
Helmick, CG
DOI：
10.1016/j.bbrc.2009.12.138
发表时间：
2010-01-29
影响因子：
3.1
作者：
Cairns, Dana M.;Uchimura, Tomoya;Kwon, Heenam;Lee, Philip G.;Seufert, Christopher R.;Matzkin, Elizabeth;Zeng, Li
通讯作者：
Zeng, Li
影响因子：
27.4
作者：
Goldring MB;Otero M;Tsuchimochi K;Ijiri K;Li Y
通讯作者：
Li Y
影响因子：
--
作者：
Hofmann, Sandra;Knecht, Sven;Meinel, Lorenz
通讯作者：
Meinel, Lorenz