Augmenting MNK1/2 activation by c-FMS proteolysis promotes osteoclastogenesis and arthritic bone erosion

作     者：Se Hwan Mun Seyeon Bae Steven Zeng Brian Oh Carmen Chai Matthew Jundong Kim Haemin Kim George Kalliolias Chitra Lekha Dahia Younseo Oh Tae-Hwan Kim Jong Dae Ji Kyung-Hyun Park-Min Se Hwan Mun;Seyeon Bae;Steven Zeng;Brian Oh;Carmen Chai;Matthew Jundong Kim;Haemin Kim;George Kalliolias;Chitra Lekha Dahia;Younseo Oh;Tae-Hwan Kim;Jong Dae Ji;Kyung-Hyun Park-Min

作者机构：Arthritis and Tissue Degeneration ProgramDavid Z.Rosensweig Genomics Research CenterNew YorkNYUSA Tissue EngineeringRegeneration and RepairHospital for Special SurgeryNew YorkNYUSA Department of Cell and Developmental BiologyWeill Cornell Medical CollegeNew YorkNYUSA BCMB allied programWeill Cornell Graduate School of Medical SciencesNew YorkNYUSA Hanyang University Institute for Rheumatology ResearchSeoulKorea Department of RheumatologyHanyang University Hospital for Rheumatic DiseasesSeoulKorea RheumatologyCollege of MedicineKorea UniversitySeoulKorea Department of MedicineWeill Cornell Medical CollegeNew YorkNYUSA 

出 版 物：《Bone Research》 (骨研究（英文版）)

年 卷 期：2021年第9卷第4期

页      面：571-581页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：This work was supported by the National institute of Arthritis and Musculoskeletal and Skin Diseases(NIAMS)of the NIH under Award Numbers R01 AR069562 and AR073156(to K.H.P.-M.) 

主　　题：osteoclast stimulating 1/2 

摘      要：Osteoclasts are bone-resorbing cells that play an essential role in homeostatic bone remodeling and pathological bone *** colony stimulating factor(M-CSF)is abundant in rheumatoid arthritis(RA).However,the role of M-CSF in arthritic bone erosion is not completely ***,we show that M-CSF can promote osteoclastogenesis by triggering the proteolysis of c-FMS,a receptor for M-CSF,leading to the generation of FMS intracellular domain(FICD)*** levels of FICD fragments positively regulated osteoclastogenesis but had no effect on inflammatory ***,myeloid cell-specific FICD expression in mice resulted in significantly increased osteoclast-mediated bone resorption in an inflammatory arthritis *** FICD formed a complex with DAP5,and the FICD/DAP5 axis promoted osteoclast differentiation by activating the MNK1/2/EIF4E pathway and enhancing NFATcl protein ***,targeting the MNK1/2 pathway diminished arthritic bone *** results identified a novel role of c-FMS proteolysis in osteoclastogenesis and the pathogenesis of arthritic bone erosion.