Nerve Growth Factor Receptor Limits Inflammation to Promote Remodeling and Repair of Osteoarthritic Joints.
Nerve Growth Factor Receptor Limits Inflammation to Promote Remodeling and Repair of Osteoarthritic Joints.
复制标题
神经生长因子受体限制炎症，促进骨关节炎关节的重塑和修复。
DOI：
10.1101/2023.12.21.572937
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Huang,Jian
中科院分区：
文献类型：
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作者：
Zhao,Lan;Lai,Yumei;Jiao,Hongli;Huang,Jian
骨关节炎(OA)是一种痛苦的、不治之症，影响着超过5亿人。最近对神经生长因子(NGF)抑制剂在骨性关节炎患者中的临床试验表明，NGF抑制对关节结构有不良影响。在此，我们报道了神经生长因子受体(NGFR)在骨性关节炎的骨骼细胞中表达上调，并在骨关节炎关节的重塑和修复中发挥重要作用。神经生长因子受体在骨软骨细胞中表达，但在骨祖细胞中不表达，并由肿瘤坏死因子α诱导，以减弱NF-κB的激活，维持适当的骨形态发生蛋白-Smad1信号转导，并抑制RANKL在小鼠体内的表达。神经生长因子受体缺乏使小鼠骨关节炎关节中的核因子-κB过度激活，从而损害骨形成并增强骨吸收，表现为软骨下骨和骨赘的减少。在人骨关节炎软骨中，神经生长因子受体与核因子-κB的激活也呈负相关。总之，这项研究表明NGFR在限制炎症修复病变骨骼组织方面的作用。
Osteoarthritis (OA) is a painful, incurable disease affecting over 500 million people. Recent clinical trials of the nerve growth factor (NGF) inhibitors in OA patients have suggested adverse effects of NGF inhibition on joint structure. Here we report that nerve growth factor receptor (NGFR) is upregulated in skeletal cells during OA and plays an essential role in the remodeling and repair of osteoarthritic joints. Specifically, NGFR is expressed in osteochondral cells but not in skeletal progenitor cells and induced by TNFα to attenuate NF-κB activation, maintaining proper BMP-SMAD1 signaling and suppressing RANKL expression in mice. NGFR deficiency hyper-activates NF-κB in murine osteoarthritic joints, which impairs bone formation and enhances bone resorption as exemplified by a reduction in subchondral bone and osteophytes. In human OA cartilage, NGFR is also negatively associated with NF-κB activation. Together, this study suggests a role of NGFR in limiting inflammation for repair of diseased skeletal tissues.