IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis

Jo, Sungsin,Wang, Sung Eun,Lee, Young Lim,Kang, Suman,Lee, Bitnara,Han, Jinil,Sung, Il-Hoon,Park, Ye-Soo,Bae, Sang-Cheol,Kim, Tae-Hwan BioMed Central 2018 Arthritis research & therapy Vol.20 No.-

<P><B>Background</B></P><P>IL-17A has recently emerged as a potential target that regulates the extensive inflammation and abnormal bone formation observed in ankylosing spondylitis (AS). Blocking IL-17A is expected to inhibit bony ankylosis. Here, we investigated the effects of anti IL-17A agents in AS.</P><P><B>Methods</B></P><P>TNFα, IL-17A, and IL-12/23 p40 levels in serum and synovial fluid from patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), osteoarthritis (OA), or healthy controls (HC) were measured by ELISA. Bone tissue samples were obtained at surgery from the facet joints of ten patients with AS and ten control (Ct) patients with noninflammatory spinal disease. The functional relevance of IL-17A, biological blockades, Janus kinase 2 (JAK2), and non-receptor tyrosine kinase was assessed in vitro with primary bone-derived cells (BdCs) and serum from patients with AS.</P><P><B>Results</B></P><P>Basal levels of IL-17A and IL-12/23 p40 in body fluids were elevated in patients with AS. JAK2 was also highly expressed in bone tissue and primary BdCs from patients with AS. Furthermore, addition of exogenous IL-17A to primary Ct-BdCs promoted the osteogenic stimulus-induced increase in ALP activity and mineralization. Intriguingly, blocking IL-17A with serum from patients with AS attenuated ALP activity and mineralization in both Ct and AS-BdCs by inhibiting JAK2 phosphorylation and downregulating osteoblast-involved genes. Moreover, JAK2 inhibitors effectively reduced JAK2-driven ALP activity and JAK2-mediated events.</P><P><B>Conclusions</B></P><P>Our findings indicate that IL-17A regulates osteoblast activity and differentiation via JAK2/STAT3 signaling. They shed light on AS pathogenesis and suggest new rational therapies for clinical AS ankylosis.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (10.1186/s13075-018-1582-3) contains supplementary material, which is available to authorized users.</P>

A novel role for bone-derived cells in ankylosing spondylitis: Focus on IL-23

Jo, Sungsin,Koo, Bon San,Lee, Bitnara,Kwon, Eunji,Lee, Young Lim,Chung, Heekyoung,Sung, Il-Hoon,Park, Ye-Soo,Kim, Tae-Hwan Elsevier 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>The main aim of this study are to explore the role of bone-derived cells (BdCs) in ankylosing spondylitis (AS) and determine the underlying molecular mechanisms of IL-23 production. Primary BdCs were isolated from diced bone of facet joints obtained during surgery from seven AS patients and seven disease control (Ct) patients. Osteoblastic activity of BdCs was assessed by measuring their alkaline phosphatase activity and by alizarin red staining. Osteoblast and endoplasmic reticulum (ER) stress-related genes were assessed by quantitative PCR, immunoblotting, immunofluorescence, and immunohistochemistry. In addition, expression of IL-23 in response to BIX (selective BIP inducer X)-induced ER stress was evaluated by qPCR and ELISA. Protein interaction and binding to IL-23 promoter were confirmed by Immunoprecipitation and Chromatin immunoprecipitation, respectively. Transcript levels of genes involved in osteoblast function, as well as of the ER stress marker were higher in the AS group than the Ct group, and elevated RUNX2, BiP and IL-23 expression were observed in the BdCs, serum, and bone biopsies from the AS group. BIX-induced ER stress stimulated osteoblastic activity and IL-23 secretion by upregulating RUNX2 expression. Furthermore, in AS BdCs, RUNX2 interacted with C/EBPβ to bind to IL-23 promoter and RUNX2 knockdown suppressed IL-23 secretion. These finding may provide a molecular mechanism involved in sustained ER stress in AS BdCs stimulates the activation of RUNX2 and C/EBPβ genes, leading to IL-23 production.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Bones and its-derived cells from patients with AS showed an increase in ER stress. </LI> <LI> IL-23 cytokine was significantly higher in AS patients than in healthy controls. </LI> <LI> Inducing ER stress in AS exhibited an increase of bone-related genes. </LI> <LI> Inducing ER stress in AS was accompanied with augmentation of IL-23 cytokine. </LI> <LI> ER stress-induced RUNX2 is involved in IL-23 secretion and bone-related genes. </LI> </UL> </P>

일부 한약재의 동종항원에 대한 세포증식 및 살세포반응 억제효과

정영란(Young-Ran Jeong),하미혜(Mee-Hye Ha),김성호(Sung-Ho Kim),조성기(Sung-Kee Jo),변명우(Myung-Woo Byun),조현욱(Hyun-Wook Cho),서권일(Kwon-Il Seo),이성태(Sung-Tae Yee) 한국식품영양과학회 2000 한국식품영양과학회지 Vol.29 No.6

본 실험에서는 동양에서 예로부터 민간요법이나 한방에서 주로 많이 쓰여지고 있는 8가지 종류의 한약재에 대해서 면역억제제로써 사용 가능성을 실험하였다. 그 결과 당귀, 산사, 어성초, 오가피, 황기의 추출물은 동종항원에 반응하는 순수분리 T세포의 증식을 농도 의존적으로 억제시켰다. 또한 이들 T세포의 증식에 있어서 필수적인 IL-2를 포함한 cytokine 즉, IL-2, IL-4, IL-10, IFN-γ의 생산량은 대조군에 비해 실험군에서 유의한 차이가 없었고 특히 T세포 증식에 필수적인 IL-2의 생산량의 변화가 거의 없었다. 이는 한약재에 의한 T세포의 증식억제 효과가 T세포증식에 필수적인 IL-2의 생산량을 억제하기 때문에 일어나는 결과가 아님을 알 수 있었다. 그리고 T세포의 살세포작용 억제를 직접적으로 측정하기 위하여 세포내 LDH의 양을 조사한 결과 모든 대조군에서 50%이상의 살세포작용 억제가 일어났고, 그중 특히 오가피와 황기에서는 100% 살세포작용 억제가 일어났다. 따라서 본 실험에 사용된 당귀, 산사, 어성초, 오가피, 황기 등의 5가지 약재가 부작용 없는 면역억제로써 사용 가능성이 높은 것으로 생각된다. In this experiment, we showed the immunosuppressive effects of herbal plant extracts on the alloantigen reactive proliferation and cytotoxicity. The extracts of Angelica gigas, Crataegus pinnatifida, Houttuynia cordata, Acanthopanax sessiliflorum and Astragalus membranaceus markedly suppressed on the pro- liferation of primary T cells stimulated with allogeneic spleen cells in a dose-dependent manner. The production of IL-2, IFN-γ, IL-4 and IL-10 in the alloreactive primary T cells showed no significant difference in the presence or absence of herbal plants extracts. Also the result of mixed lymphocyte reaction (MLR)-induced cytotoxic T lymphocyte (CTL) showed what is above a certain point 50% inhibition. Specially, the extracts of Acanthopanax sessiliflorum and Astragalus membranaceus com- pletely suppressed the killing activity of CTL. Theses results suggest that the extracts of 5 herbal plants can be used as immunosuppressive agents.

Effect of Cytokines and bFGF on the Osteoclast Differentiation Induced by 1α,25-(OH)<SUB>2</SUB>D<SUB>3</SUB> in Primary Murine Bone Marrow Cultures

Han-Jung Chae,Jang-Sook Kang,Byung-Gwan Bang,Seoung-Bum Cho,Jo-IL Han,Joo-Young Choi,Hyung-Min Kim,Soo-Wan Chae,Hyung Ryong Kim 대한생리학회-대한약리학회 1999 The Korean Journal of Physiology & Pharmacology Vol.3 No.6

<P> Bone is a complex tissue in which resorption and formation continue throughout life. The bone tissue contains various types of cells, of which the bone forming osteoblasts and bone resorbing osteoclasts are mainly responsible for bone remodeling. Periodontal disease represents example of abnormal bone remodeling. Osteoclasts are multinucleated cells present only in bone. It is believed that osteoclast progenitors are hematopoietic origin, and they are recruited from hematopoietic tissues such as bone marrow and circulating blood to bone. Cells present in the osteoclast microenvironment include marrow stromal cells, osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells produce cytokines that can affect osteoclast formation. In vitro model systems using bone marrow cultures have demonstrated that IL-1β, IL-3, TNF-α, bFGF can stimulate the formation of osteoclasts. In contrast, IL-4 inhibits osteoclast formation. Knowledge of cytokines and bFGF that affect osteoclast formation and their capacity to modulate the bone-resorbing process should provide critical insights into normal calcium homeostasis and disorders of bone turnover such as periodontal disease, osteoporosis and Paget s disease.

중국에서의 한글 연구

조일영 한국교원대학교 한국어문교육연구소 1998 한국어문교육 Vol.7 No.-

Matlab을 이용한 유성음 성도단면의 실시간 분석기 구현

권오영,박일서,조철우 국립7개대학공동논문집간행위원회 2003 공업기술연구 Vol.3 No.-

In this paper we tried to compute the shape of the vocal tract from the input speech in real-time. To implement the real-time process MATLAB Data Acquisition Toolbox was used. Implemented program can compute and display the shape of the vocal tract from the various input speech signal.

EVA Nanocomposites 제조 및 특성연구

김영용,박일수,정효선,최재곤,김정규,조병욱 조선대학교 생산기술연구소 2003 生産技術硏究 Vol.25 No.1

Ethylene vinyl acetate random copolymer(EVA)/layered-silicate nanocomposites were prepared by melt or solution blending. The TGA thermograms of EVA/ layered-silicate nanocomposites showed an improved thermal stability as the layered-silicate contents increased. The decomposition temperature of nanocomposite was increased around 10℃ compared with pure EVA at 50% weight loss under N_2 atmosphere And in an air atmosphere, temperature difference in 50% wt loss between the nanocomposlte and the virgin EVA was around 100℃ The moduli in their thermomechanical module of nanocomposite are higher than pure EVA. Interlayered spacings of nanosilicates were slightly increased when prepared by melt blending. On the other hand, they were remarkably increased when prepared by solution blending. It may be explained that EVA moiety of the copolymer showed partial adsorption behavior on the surface layer of the silicate. It also revealed that the adsorption is more effective in the solution blending than in the melt blending.

강제운동과 수면방해의 편성이 쥐에 미치는 영향 : Combined Effects Started From Childhood on Cells on Bronchoalveolar Lavage Fluids

육조영,이신언,임정일 한국스포츠리서치 2004 한국 스포츠 리서치 Vol.15 No.1

Phagocytic cells, polymorphonuclear peucocytes and macrophage, play an important role in a non-specific cellular immunity which is first defence line for infectious disease. The purpose of this paper is to clairfy combined effects of stressful exercise and sleep disturbance on rat non-specific cellular immunity represented by yields of cells from bronchoalveolar lavage and superoxide generating capacity of alveolar mecrophage. Male Wistar rats(5 weeks old) were divided into following 4 groups. 1) Training group: exercised on a treadmill at a belt speed of 35m/min for 45min/day. 2) Jet Lag group; noninvasive sleep disturbance by the shifted day/night time every 2 week interval. 3) Training+Jet Lag(T+L) group; exercised on a treadmill with sleep disturbance, that we assumed one of chronic fatigue model in this paper, and 4) Control group; set sedentary condition. After 6 weeks of the experiment, 2 groups were newly selected from T+J group for the examination of rest effects on the chronic fatigue model rats. And to examine the combined effects of stressful exercise and sleep disturbance on matured rats(11 weeks old), Acute Training + Jet Lag(AT+J) group was selected from the Control group. Rats were sacrificed at 11 and 17 weeks old. T+J group seemed to be able to adapt first 6 weeks but negative effects were found out at 17 weeks old. Same phenomena were also recognized in AT+J group. These results suggest that the chronic fatigue model rats may easily catch the infectious disease and there are possibility that both stress, stressful exercise and sleep disturbance, negatively affects the non-specific cellular immunity, especially after maturation. (육조영(2001), Hardesty(1993); Thepen(1994); Hoffman(1994))

유아 운동 프로그램 참가에 대한 부모의 발달기대 분석

김석일,신범철,육조영 한국스포츠리서치 2004 한국 스포츠 리서치 Vol.15 No.6

The purpose of this study was to examine the mothers' developmental expectancy toward their child taking part in the motor programs. The subjects were 185 mothers having children at the age of three to six who were participating in the motor programs in the sports clubs. The subjects answered a questionnaire consisting of 35 items about the developmental expectancy. The main results can be summarized as follows: 1) Factor analysis with normal varimax rotation to the questionnaire revealed the developmental expectancy consists of seven factors;general development, competence/ mastery, courtesy, autonomy, cooperation, social skills, health/ fitness. 2) The mothers who have a lower age child scored significantly high on the fifth subscale(cooperation), while there was no differences in the other subscales. And the sports experiences of mothers only related to cooperation.

잉어의 심박수 변화에 의한 스트로보광의 자극효과 판정

안영일,조현정 도립 강원전문대학 2000 道立 江原專門大學 論文集 Vol.3 No.-

The stimulating effect of strobe light to carp Cyprinus carpio was examined for the analysis of the heart rate change under difference flash frequencies. Heart rate change was clearly observed to increase during strobe flashing, with a tendency of sudden decrease immediately after the starting and ending of stimulus. The observation was repeated three times for each individual with an interval of two hours rest. The data analysis was focused to discuss the stimulating effect of strobe light with flash frequencies among 1.7-25Hz, as well as the habituation influence to the repeated trials. Under this test condition, the flash frequency of 1.7Hz produced the strongest effect of strobe stimulus. The stimulating effect decreased with the repeated trials. The retinal light adaptation process to the strobe light was slightly slower at flash frequency of 25Hz.