Insulin-Like Growth Factor II (IGF-II) Inhibits IL-1β-Induced Cartilage Matrix Loss and Promotes Cartilage Integrity in Experimental Osteoarthritis.
Insulin-Like Growth Factor II (IGF-II) Inhibits IL-1β-Induced Cartilage Matrix Loss and Promotes Cartilage Integrity in Experimental Osteoarthritis.
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DOI：
10.1002/jcb.25232
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发表时间：
2015-12
影响因子：
4
通讯作者：
Zeng L
中科院分区：
文献类型：
--
作者：
Uchimura T;Foote AT;Smith EL;Matzkin EG;Zeng L
骨关节炎（OA）是一种广泛存在的慢性关节疾病，其特征是关节软骨破坏并伴有疼痛和残疾。在这项研究中，我们发现人类 OA 患者的关节软骨以及内侧半月板不稳定的小鼠实验 OA 模型 (DMM) 中胰岛素样生长因子 II (IGF-II) 的表达减少。在原代人关节软骨细胞中，慢病毒 IGF-II 的异位表达抑制促炎细胞因子 IL-1β 诱导的 NF-κB 激活以及分解代谢基因表达。有趣的是，IGF-II 并没有显着改变 ERK1/2 或 Akt 的磷酸化状态，而 ERK1/2 或 Akt 是通常由 IGF-I 激活的激酶。相反，它诱导磷脂酶 C (PLC) 的活性，并且 PLC 抑制剂阻断 IGF-II 对 IL-1β 的抑制活性，表明这种活性是通过 PLC 介导的。此外，在体外移植的人 OA 软骨培养物中，IGF-II 增加了软骨基质水平并降低了 MMP13 蛋白表达。在体内 DMM 模型中，关节内注射慢病毒 IGF-II 导致软骨基质水平增强、MMP13 蛋白表达减少、骨赘形成和软骨下骨硬化减少。因此，我们的结果表明 IGF-II 可以促进软骨完整性并阻止 OA 中的膝关节破坏。
Osteoarthritis (OA) is a widespread chronic joint disease characterized by articular cartilage destruction and accompanied by pain and disability. In this study, we found that the expression of Insulin-like Growth Factor II (IGF-II) was reduced in articular cartilage in human OA patients as well as in the murine experimental OA model of destabilization of the medial meniscus (DMM). In primary human articular chondrocytes, ectopic expression of lentiviral IGF-II inhibited pro-inflammatory cytokine IL-1β-induced NF-κB activation as well as catabolic gene expression. Interestingly, IGF-II did not significantly alter the phosphorylation states of ERK1/2 or Akt, which are kinases typically activated by IGF-I. Instead, it induced the activity of phospholipase C (PLC) and a PLC inhibitor blocked the inhibitory activity of IGF-II against IL-1β, suggesting that this activity is mediated through PLC. Furthermore, IGF-II increased cartilage matrix levels and decreased MMP13 protein expression in explanted human OA cartilage cultures in vitro. In the in vivo DMM model, intraarticular injection of lentiviral IGF-II led to enhanced cartilage matrix levels and decreased MMP13 protein expression, as well as reduced osteophyte formation and subchondral bone sclerosis. Therefore, our results suggest that IGF-II can promote cartilage integrity and halt knee joint destruction in OA.
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影响因子：
2.8
作者：
Matsukura, Yu;Muneta, Takeshi;Tsuji, Kunikazu;Miyatake, Kazumasa;Yamada, Jun;Abula, Kahaer;Koga, Hideyuki;Tomita, Makoto;Sekiya, Ichiro
通讯作者：
Sekiya, Ichiro
影响因子：
3.2
作者：
Burg-Golani, Tamar;Pozniak, Yair;Herskovits, Anat A.
通讯作者：
Herskovits, Anat A.
影响因子：
5.8
作者：
Matsumoto, T;Gargosky, SE;Rosenfeld, RG
通讯作者：
Rosenfeld, RG
影响因子：
64.5
作者：
BAKER, J;LIU, JP;EFSTRATIADIS, A
通讯作者：
EFSTRATIADIS, A
影响因子：
4.8
作者：
Bhakta, NR;Garcia, AM;Morales, TI
通讯作者：
Morales, TI