HMGB1 expression and release by bone cells
HMGB1 expression and release by bone cells
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DOI：
10.1002/jcp.20577
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发表时间：
2006-05-01
影响因子：
5.6
通讯作者：
Bidwell, JP
中科院分区：
文献类型：
--
作者：
Charoonpatrapong, K;Shah, R;Bidwell, JP
免疫细胞和骨细胞通过两种组织共有的促炎细胞因子细胞间信号传导网络在功能上偶联，并且它们的串扰可能有助于某些免疫相关骨病理的病因学。例如，NF-κ B配体的受体激活剂（RANKL）/骨保护素（OPG）/NF-κ B的受体激活剂（RANK）信号传导轴在树突状细胞（DC）功能以及骨重建中起关键作用。免疫细胞表达RANKL可能导致牙周炎、关节炎和多发性骨髓瘤的骨丢失。最近的发现表明，DC释放染色质蛋白高迁移率族蛋白1（HMGB 1）作为一种有效的免疫调节细胞因子，介导DC和T细胞之间的相互作用，通过HMGB 1结合到晚期糖基化终产物（AGEs）的膜受体。为了确定成骨细胞或破骨细胞是否表达和/或释放HMGB 1到骨微环境中，我们分析了组织，细胞和培养基中是否存在这种分子。我们的免疫组织化学和免疫细胞化学分析表明，HMGB 1表达在原代成骨细胞和破骨细胞，这两种细胞表达。HMGB 1在原代成骨细胞培养物和分离的破骨细胞前体和破骨细胞培养物的培养基中是可回收的。甲状旁腺激素（PTH），骨重建的调节剂，减弱原代成骨细胞和MC 3 T3-E1成骨细胞样细胞培养物中HMGB 1的释放，但在大鼠骨肉瘤细胞系UMR 106-01中增加这种释放，这两种反应主要通过腺苷酸环化酶的激活。PTH诱导的UMR细胞HMGB 1释放表现出与活化巨噬细胞相似的释放动力学。这些数据证实了骨中存在HMGB 1/HMGB 2信号传导轴。
Immune and bone cells are functionally Coupled by pro-inflammatory cytokine intercellular signaling networks common to both tissues and their crosstalk may contribute to the etiologies of some immune-associated bone pathologies. For example, the receptor activator of NF-kappa B ligand (RANKL)/osteoprotegerin (OPG)/receptor activator of NF-kappa B (RANK) signaling axis plays a critical role in dendritic cell (DC) function as well as bone remodeling. The expression of RANKL by immune cells may contribute to bone loss in periodontitis, arthritis, and multiple myeloma. A recent discovery reveals that DCs release the chromatin protein high mobility group box 1 (HMGB1) as a potent immunomodulatory cytokine mediating the interaction between DCs and T-cells, via HMGB1 binding to the membrane receptor for advanced glycation end products (RAGE). To determine whether osteoblasts or osteoclasts express and/or release HMGB1 into the bone microenvironment, we analyzed tissue, cells, and culture media for the presence of this molecule. Our immunohistochemical and immunocytochemical analyses demonstrate HMGB1 expression in primary osteoblasts and osteoclasts and that both cells express RAGE. HMGB1 is recoverable in the media of primary osteoblast Cultures and cultures of isolated osteoclast precursors and osteoclasts. Parathyroid hormone (PTH), a regulator of bone remodeling, attenuates HMGB1 release in cultures of primary osteoblasts and MC3T3-E1 osteoblast-like cells but augments this release in the rat osteosarcoma cell line UMR 106-01, both responses primarily via activation of adenylyl cyclase. PTH-induced HMGB1 discharge by UMR cells exhibits similar release kinetics as reported for activated macrophages. These data confirm the presence of the HMGB1/RAGE signaling axis in bone.