Interleukin-1beta and tumor necrosis factor alpha inhibit chondrogenesis by human mesenchymal stem cells through NF-kappaB-dependent pathways.
Interleukin-1beta and tumor necrosis factor alpha inhibit chondrogenesis by human mesenchymal stem cells through NF-kappaB-dependent pathways.
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白介素-1beta和肿瘤坏死因子α通过NF-kappab依赖性途径抑制人间质干细胞的软骨发生。
DOI：
10.1002/art.24352
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发表时间：
2009-03
影响因子：
--
通讯作者：
Porter, R. M.
中科院分区：
文献类型：
--
作者：
Wehling, N.;Palmer, G. D.;Pilapil, C.;Liu, F.;Wells, J. W.;Mueller, P. E.;Evans, C. H.;Porter, R. M.
间充质干细胞（MSCs）向软骨细胞的分化为关节软骨的修复和再生提供了有吸引力的基础。在临床条件下，软骨形成通常需要在损伤或疾病反应产生的炎症介质存在的情况下发生。在这里，我们研究了两种重要的炎症细胞因子，白细胞介素-1β (IL-1β)和肿瘤坏死因子-α (TNF-α)对人间充质干细胞成软骨行为的影响。使用从股髓间管中恢复的MSCs的聚集培养物。通过定量RT-PCR检测相关转录物的表达，并通过组织学和免疫组织化学检查聚集物来评估软骨形成。通过腺病毒载体传递荧光素酶报告基因构建体和NF-κB显性阴性抑制剂（sri -κB），研究了NF-κB可能参与介导IL-1β的作用。IL-1β和TNF-α均以剂量依赖性方式抑制软骨形成。这与NF-κB的显著活化有关。sri -κB的传递消除了NF-κB的激活，恢复了软骨生成反应。尽管X型胶原的表达遵循这种模式，但其他肥厚分化标志物的反应不同。IL-1β诱导基质金属蛋白酶-13的表达依赖于NF-κB。而碱性磷酸酶活性则被IL-1β抑制，与sri - κ b是否传递无关。关节软骨损伤的细胞修复在发炎的关节中会受到损害。在这些条件下实现修复的策略包括使用单个热原的特异性拮抗剂，如IL-1和TNF，或靶向重要的细胞内介质，如NF-κB。
The differentiation of mesenchymal stem cells (MSCs) into chondrocytes provides an attractive basis for the repair and regeneration of articular cartilage. Under clinical conditions, chondrogenesis will often need to occur in the presence of inflammatory mediators produced in response to injury or disease. Here we examine the effect of two important inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), on the chondrogenic behavior of human MSCs. Aggregate cultures of MSCs recovered from the femoral intermedullary canal were used. Chondrogenesis was assessed by the expression of relevant transcripts by quantitative RT-PCR and examination of aggregates by histology and immunohistochemistry. The possible involvement of NF-κB in mediating the effects of IL-1β was examined by delivering a luciferase reporter construct and a dominant negative inhibitor of NF-κB (srIκB), with adenovirus vectors. Both IL-1β and TNF-α inhibited chondrogenesis in a dose-dependent manner. This was associated with a marked activation of NF-κB. Delivery of srIκB abrogated the activation of NF-κB and rescued the chondrogenic response. Although expression of type X collagen followed this pattern, other markers of hypertrophic differentiation responded differently. Matrix metalloproteinase-13 was induced by IL-1β in a NF-κB dependent fashion. Alkaline phosphatase activity, in contrast, was inhibited by IL-1β regardless of srIκB delivery. Cell-based repair of lesions in articular cartilage will be compromised in inflamed joints. Strategies for enabling repair under these conditions include the use of specific antagonists of individual pyrogens, such as IL-1 and TNF, or the targeting of important intracellular mediators, such as NF-κB.
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影响因子：
3.5
作者：
Gouze, JN;Bianchi, A;Bordji, K
通讯作者：
Bordji, K
影响因子：
12.4
作者：
Palmer, GD;Steinert, A;Ghivizzani, SC
通讯作者：
Ghivizzani, SC
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
2.8
作者：
Céleste, C;Ionescu, M;Laverty, S
通讯作者：
Laverty, S
影响因子：
--
作者：
Bauge, C.;Attia, J.;Boumediene, K.
通讯作者：
Boumediene, K.