HMGB proteins and arthritis.
HMGB proteins and arthritis.
复制标题
DOI：
10.1007/s13577-017-0182-x
复制
发表时间：
2018-01
期刊：
影响因子：
4.3
通讯作者：
Lotz M
中科院分区：
文献类型：
--
作者：
Taniguchi N;Kawakami Y;Maruyama I;Lotz M
高迁移率族蛋白(HMGB)家族包括四个成员：HMGB1、2、3和4。HMGB蛋白具有两种功能。在细胞核中，HMGB蛋白以DNA结构依赖但核苷酸序列不依赖的方式与DNA结合，在染色质重塑中发挥作用。在细胞外，HMGB蛋白起到警报的作用，是在组织损伤时释放的内源性分子，以激活免疫系统。HMGB1是一种晚期炎症介质，对类风湿关节炎患者的长期和持续的全身炎症起作用。相比之下，HMGB2−/−小鼠代表了一种与软骨HMGB2表达抑制相关的衰老相关骨关节炎(OA)模型。Hmgb2突变小鼠不仅发生早发性骨性关节炎，而且在关节软骨浅层(SZ)表现出一种特殊的表型。由于HMGB2和β-catenin在关节软骨中的表达和激活模式相似，关节软骨SZ中这些通路的缺失可能导致基因表达改变、细胞死亡和类骨关节炎发病。此外，HMGB2通过介导Runt相关转录因子2的表达和Wnt信号转导来调节软骨细胞肥大。因此，HMGB2调节依赖于淋巴增强因子1(LEF1)的反式激活的一个可能机制是HMGB2与核因子之间的不同相互作用影响含有LEF1反应元件的基因的转录。HMGB蛋白的多种功能揭示了这些蛋白作为关节炎症的先天和内源性调节因子的复杂作用，以及它们在软骨肥大和维持关节组织内稳中的协同作用。
The high-mobility group box (HMGB) family includes four members: HMGB1, 2, 3 and 4. HMGB proteins have two functions. In the nucleus, HMGB proteins bind to DNA in a DNA structure-dependent but nucleotide sequence-independent manner to function in chromatin remodeling. Extracellularly, HMGB proteins function as alarmins, which are endogenous molecules released upon tissue damage to activate the immune system. HMGB1 acts as a late mediator of inflammation and contributes to prolonged and sustained systemic inflammation in subjects with rheumatoid arthritis. By contrast, Hmgb2−/− mice represent a relevant model of aging-related osteoarthritis (OA), which is associated with the suppression of HMGB2 expression in cartilage. Hmgb2 mutant mice not only develop early-onset OA but also exhibit a specific phenotype in the superficial zone (SZ) of articular cartilage. Given the similar expression and activation patterns of HMGB2 and β-catenin in articular cartilage, the loss of these pathways in the SZ of articular cartilage may lead to altered gene expression, cell death and OA-like pathogenesis. Moreover, HMGB2 regulates chondrocyte hypertrophy by mediating Runt-related transcription factor 2 expression and Wnt signaling. Therefore, one possible mechanism explaining the modulation of lymphoid enhancer binding factor 1 (LEF1)-dependent transactivation by HMGB2 is that a differential interaction between HMGB2 and nuclear factors affects the transcription of genes containing LEF1-responsive elements. The multiple functions of HMGB proteins reveal the complex roles of these proteins as innate and endogenous regulators of inflammation in joints and their cooperative roles in cartilage hypertrophy as well as in the maintenance of joint tissue homeostasis.
登录
查看更多内容
影响因子：
30.8
作者：
Calogero, S;Grassi, F;Bianchi, ME
通讯作者：
Bianchi, ME
DOI：
10.1083/jcb.201608026
发表时间：
2016-11-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Aird KM;Iwasaki O;Kossenkov AV;Tanizawa H;Fatkhutdinov N;Bitler BG;Le L;Alicea G;Yang TL;Johnson FB;Noma KI;Zhang R
通讯作者：
Zhang R
影响因子：
3.7
作者：
Drissi, H;Pouliot, A;van Wijnen, AJ
通讯作者：
van Wijnen, AJ
骨关节炎的炎症。
影响因子：
5.1
作者：
Goldring MB;Otero M
通讯作者：
Otero M
影响因子：
11.8
作者：
Day, TF;Guo, XZ;Yang, YZ
通讯作者：
Yang, YZ