Is HMGB1 an osteocyte alarmin?
Is HMGB1 an osteocyte alarmin?
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DOI：
10.1002/jcb.21572
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发表时间：
2008-04-15
影响因子：
4
通讯作者：
Robling, Alexander G.
中科院分区：
文献类型：
--
作者：
Bidwell, Joseph P.;Yang, Jieping;Robling, Alexander G.
骨细胞是成骨细胞谱系的终末分化细胞，它们嵌入骨中并调节骨重建，其死亡对正常和病理性骨吸收都具有重要意义。凋亡的骨细胞会释放一种号角信号，促进破骨细胞的发育，并将其迁移到骨细胞网络的缺口。这种现象被认为是骨微损伤正常修复的基础，并有助于炎症性骨丢失的病因。染色质蛋白高迁移率族蛋白盒1蛋白（HMGB 1）已被鉴定为其他组织中的“警报素”。alarmin是由死亡和垂死细胞释放的内源性分子，其警告先天免疫系统损伤和组织修复的需要。Wang及其同事在1999年的一项具有里程碑意义的研究中提供了证据，表明释放的HMGB 1是败血症的致命介质。细胞外HMGE 1是Toll样受体（TLR）和晚期糖基化终产物（AGEs）受体的配体，所有这些受体都会放大炎症。我们实验室和其他人最近的研究表明，HMGB 1是一种骨活性细胞因子。它由体外凋亡的成骨细胞（包括MLO-Y 4骨细胞样细胞）释放。细胞外HMGB 1增强成骨细胞生成性骨髓基质细胞培养物中RANKL、TNF α和IL 6的表达，并且对破骨细胞具有趋化性。在这份招股说明书中，我们将审查HMGB 1在免疫-骨界面的活性，并提出HMGB 1作为骨细胞警报素和正常重塑和炎性骨丢失的介质的作用。
The death of osteocytes, the terminally differentiated cells of the osteoblast lineage that are embedded in bone and regulate remodeling, is significant to both normal and pathological bone resorption. Apoptotic osteocytes putatively release a clarion signal that enhances the development of the bone-resorbing osteoclasts and targets their migration to the breach in the osteocyte network. This phenomenon is thought to underlie normal repair of bone microdamage and contribute to the etiologies of inflammatory bone loss. The chromatin protein high mobility group box 1 protein (HMGB1) has been identified as an "alarmin" in other tissues. An alarmin is an endogenous molecule released by dead and dying cells that alert the innate immune system to damage and the need for tissue repair. Wang and colleagues presented evidence in a landmark 1999 study showing that released HMGB1 is a lethal mediator of sepsis. Extracellular HMGE1 is a ligand for the toll-like receptors (TLRs) and for the receptor for advanced glycation end products (RAGE) all of which amplify inflammation. Recent studies by our lab and others have shown that HMGB1 is a bone-active cytokine. It is released by apoptotic osteoblasts in vitro, including the MLO-Y4 osteocyte-like cells. Extracellular HMGB1 enhances the expression of RANKL, TNF alpha, and IL6 in osteoblastogenic bone marrow stromal cell cultures, and it is chemotactic to osteoclasts. In this prospectus we will review HMGB1 activity at the immune-bone interface and propose a role for HMGB1 as an osteocyte alarmin and mediator of normal remodeling and inflammatory bone loss.