https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/354 2026-04-09T11:54:14Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61749 Title: IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS Authors: Jung, J. H.; Kim, A.; Kim, B. Y.; Song, G. G. Abstract: Background Characterizing differentially expressed genes (DEGs) of systemic lupus erythematosus (SLE) is necessary to understand immunogenic interactions, and how several key immune genes were closely associated with the susceptibility of SLE. Objectives This study aimed to identify DEGs of SLE using gene expression-based computational methodologies to analyze disease-immune interactions, which affect the development and progression of SLE. Methods Twenty-six patients with SLE and 46 healthy controls were selected from the Gene Expression Omnibus database. The significantly enriched immune and virus related gene lists were computed and visualized by using the DEGs from the Gene Set Enrichment Analysis. Quantification of 38 immune cells were performed in determining the impact of immune cells on the virus mediated immunity in SLE by using ImmQaunt algorithm. Results Thirty nine upregulated and 57 downregulated were identified in SLE patient compared to the healthy controls. Upregulated genes were significantly implicated in Gene Ontology gene sets as cytokine mediated signaling, secretion, and exocytosis in immune response pathways. In addition, these genes were enriched in hepatitis C, influenza A, measles, Epstein–Barr virus, and herpes simplex virus 1 infection in Kyoto Encyclopedia of Genes and Genomes pathways. Especially, FCGR1A, IRF7, OAS2, CAMP, MX1, OAS3, OAS1, DEFA3, ISG15, and RSAD2 were involved in virus mediated SLE mechanism, and the expression for OAS1, OAS2, and IRF7 was closely associated with the quantities of colony forming unit-monocyte and colony forming unit-granulocyte. Conclusion Identifying virus mediated SLE genes and quantifies of immune cells were used to understand the pathological process and perform early diagnosis of SLE, and will lead to clinical tools for treating SLEs in patients. 202206-01-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/60960 Title: Augmenting MNK1/2 Activation by c-FMS Proteolysis Promotes Osteoclastogenesis and Arthritic Bone Erosion Authors: Mun, Se Hwan; Bae, Seyeon; Zeng, Steven; Oh, Brian; Chai, Carmen; Kim, Matthew Jundong; Kim, Haemin; Kalliolias, George; Dahia, Chitra Lekha; Oh, Younseo; Kim, Tae-Hwan; Ji, Jong Dae; Park-Min, Kyung-Hyun Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder. Bone erosion is one of the key clinical features of RA and is closely linked to impaired mobility of patients with RA. Osteoclasts are bone-resorbing cells and play an essential role in homeo-static bone remodeling and arthritic bone erosion. However, the underlying mechanisms of arthritic bone erosion by osteoclasts have not been fully determined. In addition to inflam-matory cytokines such as tumor necrosis factor-alpha (TNF-α), macrophage colony-stimu-lating factor (M-CSF) and its receptor c-FMS have also been implicated in the pathogenesis of RA and arthritic bone erosion. In patients with RA, the level of M-CSF increases in the serum and synovial fluid, and inhibition of c-FMS activation attenuates the progression of joint inflammation and bone erosion in animal models of arthritis. Despite the importance of M-CSF in the differentiation of myeloid cells, very little is known about the molecular mechanism underlying the role of M-CSF/c-FMS in arthritic bone erosion. In this study, we identified that M-CSF can promote osteoclasts by triggering proteolysis of c-FMS, a recep-tor for M-CSF, leading to the generation of FMS IntraCellular Domain (FICD) fragments. Increased levels of FICDs positively regulated osteoclastogenesis while having no effect on inflammatory responses. To model the high expression of FICD in vivo, we generated myeloid cell-specific conditional FICD knock-in (FICDtgM) mice. Both FICDtgM male and female mice exhibited decreased bone mass compared to control mice. Moreover, myeloid cell-specific FICD expression in mice resulted in significantly increased osteoclast-mediated bone resorption in an inflammatory arthritis model. FICD formed a complex with DAP5, and the FICD/DAP5 axis promoted osteoclast differentiation by activating the MNK1/2/EIF4E pathways and enhancing NFATc1 protein expression. Accordingly, targeting MNK1/2 path-ways diminished arthritic bone erosion. Our study identified a novel role of c-FMS prote-olysis in osteoclastogenesis and the pathogenesis of arthritic bone erosion and provided a strong basis for developing a new therapeutic target for pathological bone resorption in RA. 20211001-01-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/60951 Title: Augmenting MNK1/2 Activation by c-FMS Proteolysis Promotes Osteoclastogenesis and Arthritic Bone Erosion Authors: Mun, Se Hwan; Bae, Seyeon; Zeng, Steven; Oh, Brian; Chai, Carmen; Kim, Matthew Jundong; Kim, Haemin; Kalliolias, George; Dahia, Chitra Lekha; Oh, Younseo; Kim, Tae-Hwan; Ji, Jong Dae; Park-Min, Kyung-Hyun Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder. Bone erosion is one of the key clinical features of RA and is closely linked to impaired mobility of patients with RA. Osteoclasts are bone-resorbing cells and play an essential role in homeo-static bone remodeling and arthritic bone erosion. However, the underlying mechanisms of arthritic bone erosion by osteoclasts have not been fully determined. In addition to inflam-matory cytokines such as tumor necrosis factor-alpha (TNF-α), macrophage colony-stimu-lating factor (M-CSF) and its receptor c-FMS have also been implicated in the pathogenesis of RA and arthritic bone erosion. In patients with RA, the level of M-CSF increases in the serum and synovial fluid, and inhibition of c-FMS activation attenuates the progression of joint inflammation and bone erosion in animal models of arthritis. Despite the importance of M-CSF in the differentiation of myeloid cells, very little is known about the molecular mechanism underlying the role of M-CSF/c-FMS in arthritic bone erosion. In this study, we identified that M-CSF can promote osteoclasts by triggering proteolysis of c-FMS, a recep-tor for M-CSF, leading to the generation of FMS IntraCellular Domain (FICD) fragments. Increased levels of FICDs positively regulated osteoclastogenesis while having no effect on inflammatory responses. To model the high expression of FICD in vivo, we generated myeloid cell-specific conditional FICD knock-in (FICDtgM) mice. Both FICDtgM male and female mice exhibited decreased bone mass compared to control mice. Moreover, myeloid cell-specific FICD expression in mice resulted in significantly increased osteoclast-mediated bone resorption in an inflammatory arthritis model. FICD formed a complex with DAP5, and the FICD/DAP5 axis promoted osteoclast differentiation by activating the MNK1/2/EIF4E pathways and enhancing NFATc1 protein expression. Accordingly, targeting MNK1/2 path-ways diminished arthritic bone erosion. Our study identified a novel role of c-FMS prote-olysis in osteoclastogenesis and the pathogenesis of arthritic bone erosion and provided a strong basis for developing a new therapeutic target for pathological bone resorption in RA. 202110-01-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/43414 Title: THE INFLUENCE OF OBESITY ON TREATMENT RESPONSE TO BIOLOGIC AGENTS IN ANKYLOSING SPONDYLITIS Authors: Kim, J. H.; Ahn, G. Y.; Jung, J. H.; Choi, S. J.; Song, G. G. 202006-01-01T00:00:00Z