HMGB1 Regulates RANKL-Induced Osteoclastogenesis in a Manner Dependent on RAGE.

@article{citeulike:2446394, abstract = {Abstract High-mobility group box 1 (HMGB1), a non-histone nuclear protein, is released by macrophages into the extracellular milieu consequent to cellular activation. Extracellular HMGB1 has properties of a pro-inflammatory cytokine via its interaction with receptor for advanced glycation endproducts (RAGE) and/or toll-like receptors (TLR2 and TLR4). Although HMGB1 is highly expressed in macrophages and differentiating osteoclasts, its role in osteoclastogenesis remains largely unknown. In this report, we present evidence for a function of HMGB1 in this event. HMGB1 is released from macrophages in response to RANKL stimulation, and is required for RANKL-induced osteoclastogenesis in vitro and in vivo. In addition, HMGB1, like other osteoclastogenic cytokines (e.g., TNFalpha), enhances RANKL-induced osteoclastogenesis in vivo and in vitro at sub-threshold concentrations of RANKL, which alone would be insufficient. The role of HMGB1 in osteoclastogenesis is mediated, in large part, by its interaction with RAGE, an immunoglobin domain containing family receptor that plays an important role in osteoclast terminal differentiation and activation. HMGB1-RAGE signaling appears to be important in regulating actin cytoskeleton reorganization, thereby participating in RANKL-induced and integrin-dependent osteoclastogenesis. Taken together, these observations demonstrate a novel function of HMGB1 in osteoclastogenesis and provide a new link between inflammatory mechanisms and bone resorption.}, author = {Zhou, Zheng and Han, Jun-Yan Y. and Xi, Cai-Xia X. and Xie, Jian-Xin X. and Feng, Xu and Wang, Cong-Yi Y. and Mei, Lin and Xiong, Wen-Cheng C. }, citeulike-article-id = {2446394}, doi = {http://dx.doi.org/10.1359/jbmr.080234}, issn = {1523-4681}, journal = {J Bone Miner Res}, month = {February}, posted-at = {2008-02-29 03:23:51}, priority = {2}, title = {HMGB1 Regulates RANKL-Induced Osteoclastogenesis in a Manner Dependent on RAGE.}, url = {http://dx.doi.org/10.1359/jbmr.080234}, year = {2008} }

TY - JOUR ID - citeulike:2446394 L3 - citeulike-article-id:2446394 TI - HMGB1 Regulates RANKL-Induced Osteoclastogenesis in a Manner Dependent on RAGE. JF - J Bone Miner Res SN - 1523-4681 N2 - Abstract High-mobility group box 1 (HMGB1), a non-histone nuclear protein, is released by macrophages into the extracellular milieu consequent to cellular activation. Extracellular HMGB1 has properties of a pro-inflammatory cytokine via its interaction with receptor for advanced glycation endproducts (RAGE) and/or toll-like receptors (TLR2 and TLR4). Although HMGB1 is highly expressed in macrophages and differentiating osteoclasts, its role in osteoclastogenesis remains largely unknown. In this report, we present evidence for a function of HMGB1 in this event. HMGB1 is released from macrophages in response to RANKL stimulation, and is required for RANKL-induced osteoclastogenesis in vitro and in vivo. In addition, HMGB1, like other osteoclastogenic cytokines (e.g., TNFalpha), enhances RANKL-induced osteoclastogenesis in vivo and in vitro at sub-threshold concentrations of RANKL, which alone would be insufficient. The role of HMGB1 in osteoclastogenesis is mediated, in large part, by its interaction with RAGE, an immunoglobin domain containing family receptor that plays an important role in osteoclast terminal differentiation and activation. HMGB1-RAGE signaling appears to be important in regulating actin cytoskeleton reorganization, thereby participating in RANKL-induced and integrin-dependent osteoclastogenesis. Taken together, these observations demonstrate a novel function of HMGB1 in osteoclastogenesis and provide a new link between inflammatory mechanisms and bone resorption. AU - Zhou, Zheng AU - Han, Jun-Yan AU - Xi, Cai-Xia AU - Xie, Jian-Xin AU - Feng, Xu AU - Wang, Cong-Yi AU - Mei, Lin AU - Xiong, Wen-Cheng PY - 2008/02/26/ UR - http://dx.doi.org/10.1359/jbmr.080234 ER -