Ji-kun Qian , Yuan Ma , Xuan Huang , Xiao-ran Li , Ya-fei Xu , Zi-ying Liu , Yuan Gu , Ke Shen , Liang-jie Tian , Yu-tian Wang , Ning-ning Cheng , Bing-sheng Yang , Kui-yuan Huang , Yu Chai , Guan-qiao Liu , Nai-qian Cui , Song-yun Deng , Nan Jiang , Dao-rong Xu , Bin Yu
{"title":"CD163/TWEAK/Fn14轴：缓解炎症性骨质流失的潜在治疗靶点","authors":"Ji-kun Qian , Yuan Ma , Xuan Huang , Xiao-ran Li , Ya-fei Xu , Zi-ying Liu , Yuan Gu , Ke Shen , Liang-jie Tian , Yu-tian Wang , Ning-ning Cheng , Bing-sheng Yang , Kui-yuan Huang , Yu Chai , Guan-qiao Liu , Nai-qian Cui , Song-yun Deng , Nan Jiang , Dao-rong Xu , Bin Yu","doi":"10.1016/j.jot.2024.09.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Osteoclast (OC) over-activation is an important cause of bone loss that is strongly correlated with inflammation. Although the CD163/TWEAK/Fn14 axis has been implicated in several inflammatory pathologies, its contributions to inflammatory bone loss remain poorly understood. This study aimed to evaluate the interaction of the CD163/TWEAK/Fn14 axis with OC in inflammatory bone loss.</div></div><div><h3>Methods</h3><div>To assess the role of CD163 in bone homeostasis, we characterized the bone phenotypes of CD163-deficient mice and their wild-type littermates. CD163 and TWEAK levels were evaluated in the bone marrow of mice with LPS-induced bone loss and individuals with rheumatoid arthritis (RA). Bone mass changes were assessed using uCT and histology following supplementation with recombinant mouse CD163 protein (rCD163) or blockade of TWEAK/Fn14 signaling in CD163-deficient mice and mice with LPS-induced bone loss. The impact of CD163/TWEAK on OC differentiation and bone resorption capacity was analyzed <em>in vitro</em>.</div></div><div><h3>Results</h3><div>CD163 deficiency caused decreased bone mass and increased OC abundance. Lower CD163 expression and higher TWEAK expression were observed in the bone marrow of mice with LPS-induced bone loss and individuals with RA. TWEAK, mainly derived from CD68<sup>+</sup> macrophages, was responsible for bone loss, and supplementing rCD163 or blocking TWEAK/Fn14 signaling contributed to rescue bone loss. TWEAK/Fn14 synergistically promoted RANKL-dependent OC differentiation and bone resorption capability through downstream mitogen-activated protein kinases (MAPK) signaling, while the pro-osteoclastic effect of TWEAK was suppressed by CD163.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that the CD163/TWEAK/Fn14 axis is a potential therapeutic target for inflammatory bone loss by regulating osteoclastogenesis.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 82-95"},"PeriodicalIF":5.9000,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The CD163/TWEAK/Fn14 axis: A potential therapeutic target for alleviating inflammatory bone loss\",\"authors\":\"Ji-kun Qian , Yuan Ma , Xuan Huang , Xiao-ran Li , Ya-fei Xu , Zi-ying Liu , Yuan Gu , Ke Shen , Liang-jie Tian , Yu-tian Wang , Ning-ning Cheng , Bing-sheng Yang , Kui-yuan Huang , Yu Chai , Guan-qiao Liu , Nai-qian Cui , Song-yun Deng , Nan Jiang , Dao-rong Xu , Bin Yu\",\"doi\":\"10.1016/j.jot.2024.09.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>Osteoclast (OC) over-activation is an important cause of bone loss that is strongly correlated with inflammation. Although the CD163/TWEAK/Fn14 axis has been implicated in several inflammatory pathologies, its contributions to inflammatory bone loss remain poorly understood. This study aimed to evaluate the interaction of the CD163/TWEAK/Fn14 axis with OC in inflammatory bone loss.</div></div><div><h3>Methods</h3><div>To assess the role of CD163 in bone homeostasis, we characterized the bone phenotypes of CD163-deficient mice and their wild-type littermates. CD163 and TWEAK levels were evaluated in the bone marrow of mice with LPS-induced bone loss and individuals with rheumatoid arthritis (RA). Bone mass changes were assessed using uCT and histology following supplementation with recombinant mouse CD163 protein (rCD163) or blockade of TWEAK/Fn14 signaling in CD163-deficient mice and mice with LPS-induced bone loss. The impact of CD163/TWEAK on OC differentiation and bone resorption capacity was analyzed <em>in vitro</em>.</div></div><div><h3>Results</h3><div>CD163 deficiency caused decreased bone mass and increased OC abundance. Lower CD163 expression and higher TWEAK expression were observed in the bone marrow of mice with LPS-induced bone loss and individuals with RA. TWEAK, mainly derived from CD68<sup>+</sup> macrophages, was responsible for bone loss, and supplementing rCD163 or blocking TWEAK/Fn14 signaling contributed to rescue bone loss. TWEAK/Fn14 synergistically promoted RANKL-dependent OC differentiation and bone resorption capability through downstream mitogen-activated protein kinases (MAPK) signaling, while the pro-osteoclastic effect of TWEAK was suppressed by CD163.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that the CD163/TWEAK/Fn14 axis is a potential therapeutic target for inflammatory bone loss by regulating osteoclastogenesis.</div></div>\",\"PeriodicalId\":16636,\"journal\":{\"name\":\"Journal of Orthopaedic Translation\",\"volume\":\"49 \",\"pages\":\"Pages 82-95\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-10-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Orthopaedic Translation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2214031X2400113X\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ORTHOPEDICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Orthopaedic Translation","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2214031X2400113X","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}
The CD163/TWEAK/Fn14 axis: A potential therapeutic target for alleviating inflammatory bone loss
Objective
Osteoclast (OC) over-activation is an important cause of bone loss that is strongly correlated with inflammation. Although the CD163/TWEAK/Fn14 axis has been implicated in several inflammatory pathologies, its contributions to inflammatory bone loss remain poorly understood. This study aimed to evaluate the interaction of the CD163/TWEAK/Fn14 axis with OC in inflammatory bone loss.
Methods
To assess the role of CD163 in bone homeostasis, we characterized the bone phenotypes of CD163-deficient mice and their wild-type littermates. CD163 and TWEAK levels were evaluated in the bone marrow of mice with LPS-induced bone loss and individuals with rheumatoid arthritis (RA). Bone mass changes were assessed using uCT and histology following supplementation with recombinant mouse CD163 protein (rCD163) or blockade of TWEAK/Fn14 signaling in CD163-deficient mice and mice with LPS-induced bone loss. The impact of CD163/TWEAK on OC differentiation and bone resorption capacity was analyzed in vitro.
Results
CD163 deficiency caused decreased bone mass and increased OC abundance. Lower CD163 expression and higher TWEAK expression were observed in the bone marrow of mice with LPS-induced bone loss and individuals with RA. TWEAK, mainly derived from CD68+ macrophages, was responsible for bone loss, and supplementing rCD163 or blocking TWEAK/Fn14 signaling contributed to rescue bone loss. TWEAK/Fn14 synergistically promoted RANKL-dependent OC differentiation and bone resorption capability through downstream mitogen-activated protein kinases (MAPK) signaling, while the pro-osteoclastic effect of TWEAK was suppressed by CD163.
Conclusion
Our findings suggest that the CD163/TWEAK/Fn14 axis is a potential therapeutic target for inflammatory bone loss by regulating osteoclastogenesis.
期刊介绍：
The Journal of Orthopaedic Translation (JOT) is the official peer-reviewed, open access journal of the Chinese Speaking Orthopaedic Society (CSOS) and the International Chinese Musculoskeletal Research Society (ICMRS). It is published quarterly, in January, April, July and October, by Elsevier.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
