Pro-inflammatory Cytokines Modulating Osteoclast Differentiation and Function

( Semun Seong ),( Jung Ha Kim ),( Nacksung Kim ) 대한류마티스학회 2016 대한류마티스학회지 Vol.23 No.3

In general, bone homeostasis is maintained through the balance between bone formation and resorption. Disruption in this balance results in bone-related diseases such as osteopetrosis, osteoporosis, and rheumatoid arthritis. Often, enhanced osteoclastogenesis is followed by accelerated bone resorption that is induced by pro-inflammatory cytokines in osteoporosis or rheumatoid arthritis, and leads to bone destruction. In this review study, factors involved in osteoclast differentiation and function are discussed, and how the prevention of such factors is effective in ameliorating bone loss in osteoporosis or rheumatoid arthritis. (J Rheum Dis 2016;23:148-153)

Alternative regulatory mechanism for the maintenance of bone homeostasis via STAT5-mediated regulation of the differentiation of BMSCs into adipocytes

Seong Semun,Kim Jung Ha,Kim Kabsun,Kim In Young,Koh Jeong-Tae,Kim Nacksung 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

STAT5 is a transcription factor that is activated by various cytokines, hormones, and growth factors. Activated STAT5 is then translocated to the nucleus and regulates the transcription of target genes, affecting several biological processes. Several studies have investigated the role of STAT5 in adipogenesis, but unfortunately, its role in adipogenesis remains controversial. In the present study, we generated adipocyte-specific Stat5 conditional knockout (cKO) ( Stat5 fl/fl ;Apn-cre ) mice to investigate the role of STAT5 in the adipogenesis of bone marrow mesenchymal stem cells (BMSCs). BMSC adipogenesis was significantly inhibited upon overexpression of constitutively active STAT5A, while it was enhanced in the absence of Stat5 in vitro. In vivo adipose staining and histological analyses revealed increased adipose volume in the bone marrow of Stat5 cKO mice. ATF3 is the target of STAT5 during STAT5-mediated inhibition of adipogenesis, and its transcription is regulated by the binding of STAT5 to the Atf3 promoter. ATF3 overexpression was sufficient to suppress the enhanced adipogenesis of Stat5- deficient adipocytes, and Atf3 silencing abolished the STAT5-mediated inhibition of adipogenesis. Stat5 cKO mice exhibited reduced bone volume due to an increase in the osteoclast number, and coculture of bone marrow-derived macrophages with Stat5 cKO adipocytes resulted in enhanced osteoclastogenesis, suggesting that an increase in the adipocyte number may contribute to bone loss. In summary, this study shows that STAT5 is a negative regulator of BMSC adipogenesis and contributes to bone homeostasis via direct and indirect regulation of osteoclast differentiation; therefore, it may be a leading target for the treatment of both obesity and bone loss-related diseases.

빅데이터를 활용한 오페라 공연에 대한 소비자 인식 연구

장서문(Chang, Semun),이영희(Lee, Younghee) 건국대학교 글로컬문화전략연구소 2021 문화콘텐츠연구 Vol.- No.23

문화산업은 다른 산업들과 밀접한 관련이 있으며 고부가가치 특성을 가진다. 일반적으로 경제 수준의 향상은 문화 활동에 대한 수요를 증가시켜 문화산업의 발전으로 이어진다. 국내 오페라 공연 활성화를 위해 국가 및 단체와 예술가들이 다양한 방안을 모색하고 있으며, 특히, 관객과 더 가까워지고 보다 편안하게 다가가려는 새로운 시도들이 이루어지고 있다. 오페라 공연 활성화를 위한 효과적인 방안을 모색하기 위해서는 오페라 공연의 수요자인 소비자들의 인식을 살펴보는 것이 중요하며, 이에 대한 이해를 바탕으로 오페라 공연 활성화 전략을 체계적으로 구축해야 할 것이다. 본 연구에서는 국내 오페라의 대중화 방안을 모색하기 위하여 빅데이터 분석을 통하여 오페라에 대한 소비자 인식을 살펴보았다. 오페라 관련 빅데이터는 국내 웹사이트를 기반으로 2017년 6월부터 2020년 5월까지 3년 기간에 대한 자료를 수집하였으며, 수집된 데이터는 텍스트 마이닝 기반 키워드 빈도와 연결 중심성을 확인하였으며, 단어 간의 연결 구조와 관계를 시각화하여 살펴보았다. 또한 감성분석을 통하여 오페라 공연에 대한 소비자들의 다양한 감성적 표현을 확인하였다. 본 연구는 국가적으로 문화 콘텐츠 중심의 정책과 국민의 문화 의식 향상 및 공연예술에 대한 요구가 증대되는 시점에서 빅데이터 분석을 통하여 국내 오페라 공연의 대중화를 통한 성장전략을 소비자 중심에서 모색해 보고자 했다는 점에서 학문적, 사회적인 의의를 가지며, 본 연구에서 빅데이터를 통하여 구체적으로 확인한 오페라 공연에 대한 소비자 인식과 네트워크 관련성, 그리고 다양한 감성에 대한 분석은 국내 오페라 공연의 소비자 지향적인 활성화 전략을 수립하는데 유용한 기초 자료가 될 것으로 사료된다. The cultural industry is highly associated with other industries and has high value-added characteristics. In general, an improvement in economic standards increases the demand for cultural activities, which in turn leads to the development of the cultural industry. To revitalize domestic opera performances, many musicians and cultural organizations have sought various solutions, and new attempts have been made to get closer and easier to the audience, such as opera festivals, state-sponsored projects, small opera, visiting opera, and matinee. In order to come up with effective measures to revitalize opera performances, research on consumers who are willing to watch opera is important, and based on this, there need to be extensive business supports which should be systematic and well connected. In this study, big data analysis on consumer perception was conducted to understand how domestic operas were popularized. The collection of big data was done based on the website. The collected data was subjected to text mining-based keyword analysis, connection centrality, and sentiment analysis. Through research and analysis using big data, it is expected to be useful in establishing a consumer-centered activation strategy for domestic operas in terms of grasping consumer awareness, network relevance, and personal sensibility for opera. This study will be helpful to understand consumers" needs for opera performances and to understand them. And the research results will be used to get closer to the performance consumers.

축 압축력을 받는 원통형 얇은 소재의 좌굴후 탄소성 대변형에 관한 실험 및 해석 연구

권세문,윤희도 국립7개대학공동논문집간행위원회 2001 공업기술연구 Vol.1 No.-

circular cylindrical tubes are widely used in structures such as vehicles and aircraft structures, where light weight and high compressive/bending/torsional load carrying capacity are required. When axially compressed, relatively thick circular cylindrical tubes deform in a so-called ring mode. Each ring develops and completely collapses one by one until the entire length of the tube collapses. During the collapse process the tube absorbs a large amount of energy. Like honey-comb structures, circular cylindrical tubes are light weighted, are capable of high axial compressive load, and absorb a large amount of energy before being completely collapsed. In this report, the subject of axial plastic buckling of circular cylindrical tubes was reviewed first. Then, the axial collapse process of the tubes in a so-called ring mode was studied both experimentally and numerically. In the experiment, steel tubes were axially compressed slowly until they were completely collapsed. Fixed boundary condition was provided. Numerical study involves axisymmetric, elastic-plastic, large deflection, self-contact mechanisms. The measured and calculated results were presented and compared with each other. The purpose of the study was to evaluate the load carrying capacity and the energy absorbing capacity of the tube.

Tusc2/Fus1 regulates osteoclast differentiation through NF- κB and NFATc1

( Inyoung Kim ),( Jung Ha Kim ),( Kabsun Kim ),( Semun Seong ),( Nacksung Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.9

Tumor suppressor candidate 2 (Tusc2, also known as Fus1) regulates calcium signaling, and Ca²⁺-dependent nuclear factor of activated T-cells (NFAT) and nuclear factor kappa B (NF-кB) pathways, which play roles in osteoclast differentiation. However, the role of Tusc2 in osteoclasts remains unknown. Here, we report that Tusc2 positively regulates the differentiation of osteoclasts. Overexpression of Tusc2 in osteoclast precursor cells enhanced receptor activator of nuclear factor кB ligand (RANKL)-induced osteoclast differentiation. In contrast, small interfering RNA-mediated knockdown of Tusc2 strongly inhibited osteoclast differentiation. In addition, Tusc2 induced the activation of RANKL-mediated NF-кB and calcium/calmodulin-dependent kinase IV (CaMKIV)/cAMP-response element (CRE)-binding protein CREB signaling cascades. Taken together, these results suggest that Tusc2 acts as a positive regulator of RANKL-mediated osteoclast differentiation. [BMB Reports 2017; 50(9): 454-459]

The IRF2BP2-KLF2 axis regulates osteoclast and osteoblast differentiation

( Inyoung Kim ),( Jung Ha Kim ),( Kabsun Kim ),( Semun Seong ),( Nacksung Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2019 BMB Reports Vol.52 No.7

Kruppel-like factor 2 (KLF2) has been implicated in the regulation of cell proliferation, differentiation, and survival in a variety of cells. Recently, it has been reported that KLF2 regulates the p65-mediated transactivation of NF-κB. Although the NF-κB pathway plays an important role in the differentiation of osteoclasts and osteoblasts, the role of KLF2 in these bone cells has not yet been fully elucidated. In this study, we demonstrated that KLF2 regulates osteoclast and osteoblast differentiation. The overexpression of KLF2 in osteoclast precursor cells inhibited osteoclast differentiation by downregulating c-Fos, NFATc1, and TRAP expression, while KLF2 overexpression in osteoblasts enhanced osteoblast differentiation and function by upregulating Runx2, ALP, and BSP expression. Conversely, the downregulation of KLF2 with KLF2-specific siRNA increased osteoclast differentiation and inhibited osteoblast differentiation. Moreover, the overexpression of interferon regulatory protein 2-binding protein 2 (IRF2BP2), a regulator of KLF2, suppressed osteoclast differentiation and enhanced osteoblast differentiation and function. These effects were reversed by downregulating KLF2. Collectively, our data provide new insights and evidence to suggest that the IRF2BP2/KLF2 axis mediates osteoclast and osteoblast differentiation, thereby affecting bone homeostasis. [BMB Reports 2019; 52(7): 469-474]

IRF2 enhances RANKL-induced osteoclast differentiation via regulating NF-κB/NFATc1 signaling

( Inyoung Kim ),( Jung Ha Kim ),( Kabsun Kim ),( Semun Seong ),( Keun-bae Lee ),( Nacksung Kim ) 생화학분자생물학회 2021 BMB Reports Vol.54 No.9

Interferon regulatory factors (IRFs) play roles in various biological processes including cytokine signaling, cell growth regulation and hematopoietic development. Although it has been reported that several IRFs are involved in bone metabolism, the role of IRF2 in bone cells has not been elucidated. Here, we investigated the involvement of IRF2 in RANKL-induced osteoclast differentiation. IRF2 overexpression in osteoclast precursor cells enhanced osteoclast differentiation by regulating the expression of NFATc1, a master regulator of osteoclastogenesis. Conversely, IRF2 knockdown inhibited osteoclast differentiation and decreased the NFATc1 expression. Moreover, IRF2 increased the translocation of NF-κB subunit p65 to the nucleus in response to RANKL and subsequently induced the expression of NFATc1. IRF2 plays an important role in RANKL-induced osteoclast differentiation by regulating NF-κB/NFATc1 signaling pathway. Taken together, we demonstrated the molecular mechanism of IRF2 in osteoclast differentiation, and provide a molecular basis for potential therapeutic targets for the treatment of bone diseases characterized by excessive bone resorption. [BMB Reports 2021; 54(9): 482-487]

TRIM38 regulates NF-κB activation through TAB2 degradation in osteoclast and osteoblast differentiation

Kim, Kabsun,Kim, Jung Ha,Kim, Inyoung,Seong, Semun,Kim, Nacksung Elsevier 2018 Bone Vol.113 No.-

<P><B>Abstract</B></P> <P>The tripartite motif protein 38 (TRIM38), a member of the TRIM family, is involved in various cellular processes such as cell proliferation, differentiation, apoptosis, and antiviral defense. However, the role of TRIM38 in osteoclast and osteoblast differentiation is not yet known. In this study, we report the involvement of TRIM38 in osteoclast and osteoblast differentiation. Overexpression of TRIM38, in osteoclast precursor cells, attenuated receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation, RANKL-triggered NF-κB activation, and expression of osteoclast marker genes, such as NFATc1, osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP); and down-regulation of TRIM38 expression showed the opposite effects. Ectopic expression of TRIM38 in osteoblast precursors induced increased osteoblast differentiation and function. Elevated expression of alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin was also observed due to blockade of NF-κB activation. Conversely, knockdown of TRIM38 showed the opposite effects. TRIM38 also induced degradation of lysosome-dependent transforming growth factor beta-activated kinase 1 and MAP3K7-binding protein 2 (TAB2), further blocking NF-κB activation. Taken together, our data suggest that TRIM38 plays a critical role in bone remodeling as a negative regulator of NF-κB in both osteoclast and osteoblast differentiation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TRIM38 expression was regulated during osteoclast and osteoblast differentiation. </LI> <LI> TRIM38 negatively regulates osteoclast differentiation and activity. </LI> <LI> TRIM38 positively regulates osteoblast differentiation and function. </LI> <LI> TRIM38 regulates NF-kB activation through TAB2 degradation in osteoclasts and osteoblasts. </LI> </UL> </P>

Role of CrkII Signaling in RANKL-Induced Osteoclast Differentiation and Function

Kim, Jung Ha,Kim, Kabsun,Kim, Inyoung,Seong, Semun,Nam, Kwang-Il,Lee, Seoung Hoon,Kim, Kyung Keun,Kim, Nacksung The American Association of Immunologists, Inc. 2016 JOURNAL OF IMMUNOLOGY Vol.196 No.3

<P>Rac1, a member of small GTPases, is a key regulator of osteoclast differentiation and function. The Crk family adaptor proteins, consisting of Src homology (SH) 2 and SH3 protein-binding domains, regulate cell proliferation, migration, and invasion through Rac1 activation. In this study, we examined the role of CrkII in osteoclast differentiation and function. Retroviral overexpression of CrkII in osteoclast precursors enhanced osteoclast differentiation and resorptive function through Rac1 activation. The knockdown of CrkII in osteoclast precursors using small interfering RNA inhibited osteoclast differentiation and its resorption activity. Unlike wild-type CrkII, overexpression of the three SH domains in mutant forms of CrkII did not enhance either osteoclast differentiation or function. Phosphorylation of p130 Crk-associated substrate (p130Cas) by osteoclastogenic cytokines in preosteoclasts increased the interaction between p130Cas and CrkII, which is known to be involved in Rac1 activation. Furthermore, transgenic mice over expressing CrkII under control of a tartrate-resistant acid phosphatase promoter exhibited a low bone mass phenotype, associated with increased resorptive function of osteoclasts in vivo. Taken together, our data suggest that the p130Cas/CrkII/Rac1 signaling pathway plays an important role in osteoclast differentiation and function, both in vitro and in vivo.</P>

BCAP promotes osteoclast differentiation through regulation of the p38-dependent CREB signaling pathway

Kim, Jung Ha,Kim, Kabsun,Kim, Inyoung,Seong, Semun,Lee, Keun-Bae,Kim, Nacksung Elsevier 2018 Bone Vol.107 No.-

<P><B>Abstract</B></P> <P>Many studies have determined that PI3K-Akt signaling pathways play important roles in osteoclast differentiation and function. In the present study, we investigated the roles of B-cell adaptor for PI3K (BCAP), which is a PI3K binding molecule, in osteoclasts. Overexpression of BCAP in osteoclast precursor cells enhanced osteoclast differentiation induced by tumor necrosis factor alpha (TNF-α) as well as receptor activator of nuclear factor-κB ligand (RANKL). Conversely, osteoclast differentiation mediated by both cytokines was attenuated when BCAP expression was downregulated using small interfering RNA. Notably, BCAP induced Akt activation only upon stimulation by RANKL, but not by TNF-α. However, BCAP activated p38-dependent cAMP response element-binding protein (CREB) phosphorylation induced by both RANKL and TNF-α. Collectively, we showed that BCAP plays an important role in osteoclast differentiation by regulating the p38-dependent CREB signaling pathway, and that BCAP might be a new therapeutic target for bone diseases.</P> <P><B>Highlights</B></P> <P> <UL> <LI> BCAP positively regulates both RANKL- and TNF-α-induced osteoclast differentiation. </LI> <LI> BCAP increases the phosphorylation of Akt by RANKL, but not TNF-α. </LI> <LI> BCAP enhances both RANKL- and TNF-α-induced CREB activation. </LI> <LI> BCAP promotes osteoclast differentiation by regulating p38-dependent CREB signaling pathway rather than PI3K-Akt signaling pathway. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>