المؤلفون: Shin, Bongjin¹ (AUTHOR), Hrdlicka, Henry C.² (AUTHOR), Karki, Sangita² (AUTHOR), Fraser, Brianna² (AUTHOR), Lee, Sun‐Kyeong¹ (AUTHOR), Delany, Anne M.² (AUTHOR) adelany@uchc.edu

المصدر: Journal of Cellular Physiology. May2024, p1. 12p. 4 Illustrations, 1 Chart.

مستخلص: Osteoclasts are the cells primarily responsible for inflammation‐induced bone loss, as is particularly seen in rheumatoid arthritis. Increasing evidence suggests that osteoclasts formed under homeostatic versus inflammatory conditions may differ in phenotype. While microRNA‐29‐3p family members (miR‐29a‐3p, miR‐29b‐3p, miR‐29c‐3p) promote the function of RANKL‐induced osteoclasts, the role of miR‐29‐3p during inflammatory TNF‐α‐induced osteoclastogenesis is unknown. We used bulk RNA‐seq, histology, qRT‐PCR, reporter assays, and western blot analysis to examine bone marrow monocytic cell cultures and tissue from male mice in which the function of miR‐29‐3p family members was decreased by expression of a miR‐29‐3p tough decoy (TuD) competitive inhibitor in the myeloid lineage (LysM‐cre). We found that RANKL‐treated monocytic cells expressing the miR‐29‐3p TuD developed a hypercytokinemia/proinflammatory gene expression profile in vitro, which is associated with macrophages. These data support the concept that miR‐29‐3p suppresses macrophage lineage commitment and may have anti‐inflammatory effects. In correlation, when miR‐29‐3p activity was decreased, TNF‐α‐induced osteoclast formation was accentuated in an in vivo model of localized osteolysis and in a cell‐autonomous manner in vitro. Further, miR‐29‐3p targets mouse TNF receptor 1 (TNFR1/Tnfrsf1a), an evolutionarily conserved regulatory mechanism, which likely contributes to the increased TNF‐α signaling sensitivity observed in the miR‐29‐3p decoy cells. Whereas our previous studies demonstrated that the miR‐29‐3p family promotes RANKL‐induced bone resorption, the present work shows that miR‐29‐3p dampens TNF‐α‐induced osteoclastogenesis, indicating that miR‐29‐3p has pleiotropic effects in bone homeostasis and inflammatory osteolysis. Our data supports the concept that the knockdown of miR‐29‐3p activity could prime myeloid cells to respond to an inflammatory challenge and potentially shift lineage commitment toward macrophage, making the miR‐29‐3p family a potential therapeutic target for modulating inflammatory response. [ABSTRACT FROM AUTHOR]

المؤلفون: Huisman, Christian, Kim, Young A., Jeon, Shin, Shin, Bongjin, Choi, Jeonghoon, Lim, Su Jeong, Youn, Sung Min, Park, Younjung, K. C., Medha, Kim, Sangsoo, Lee, Soo-Kyung, Lee, Seunghee, Lee, Jae W.

المصدر: Nature Communications ; volume 12, issue 1 ; ISSN 2041-1723

مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: In humans, inactivating mutations in MLL4 , which encodes a histone H3-lysine 4-methyltransferase, lead to Kabuki syndrome (KS). While dwarfism is a cardinal feature of KS, the underlying etiology remains unclear. Here we report that Mll4 regulates the development of growth hormone-releasing hormone (GHRH)-producing neurons in the mouse hypothalamus. Our two Mll4 mutant mouse models exhibit dwarfism phenotype and impairment of the developmental programs for GHRH-neurons. Our ChIP-seq analysis reveals that, in the developing mouse hypothalamus, Mll4 interacts with the transcription factor Nrf1 to trigger the expression of GHRH-neuronal genes. Interestingly, the deficiency of Mll4 results in a marked reduction of histone marks of active transcription, while treatment with the histone deacetylase inhibitor AR-42 rescues the histone mark signature and restores GHRH-neuronal production in Mll4 mutant mice. Our results suggest that the developmental dysregulation of Mll4-directed epigenetic control of transcription plays a role in the development of GHRH-neurons and dwarfism phenotype in mice.

الإتاحة: https://doi.org/10.1038/s41467-020-20511-7Test
https://www.nature.com/articles/s41467-020-20511-7.pdfTest
https://www.nature.com/articles/s41467-020-20511-7Test

المؤلفون: Kim, Sumi, Lee, Nari, Park, Eui-Soon, Yun, Hyeongseok, Ha, Tae-Uk, Jeon, Hyoeun, Yu, Jiyeon, Choi, Seunga, Shin, Bongjin, Yu, Jungeun, Rhee, Sang Dal, Choi, Yongwon, Rho, Jaerang

المساهمون: Ministry of Education, Chungnam National University

المصدر: Molecules and Cells ; volume 44, issue 1, page 1-12 ; ISSN 1016-8478

مصطلحات موضوعية: Cell Biology, Molecular Biology, General Medicine

الإتاحة: https://doi.org/10.14348/molcells.2020.0143Test
http://pdf.medrang.co.kr/KSMCB/2021/044/KSMCB044-01-01.pdfTest
https://api.elsevier.com/content/article/PII:S1016847823001681?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1016847823001681?httpAccept=text/plainTest

المؤلفون: Yun, Hyeongseok, Park, Eui-Soon, Choi, Seunga, Shin, Bongjin, Yu, Jungeun, Yu, Jiyeon, Amarasekara, Dulshara Sachini, Kim, Sumi, Lee, Nari, Choi, Jong-Soon, Choi, Yongwon, Rho, Jaerang

المساهمون: John, Rosalind M., Ministry of Education, Ministry of National Defense, Chungnam National University

المصدر: PLOS Genetics ; volume 15, issue 6, page e1008214 ; ISSN 1553-7404

الإتاحة: https://doi.org/10.1371/journal.pgen.1008214Test

المؤلفون: Shin, Bongjin, Won, Heeyeon, Adams, Douglas J, Lee, Sun-Kyeong

المصدر: Journal of Bone and Mineral Research ; volume 35, issue 1, page 130-142 ; ISSN 0884-0431 1523-4681

مصطلحات موضوعية: Orthopedics and Sports Medicine, Endocrinology, Diabetes and Metabolism

الوصف: CD55 is a glycosylphosphatidylinositol (GPI)-anchored protein that regulates complement-mediated and innate and adaptive immune responses. Although CD55 is expressed in various cell types in the bone marrow, its role in bone has not been investigated. In the current study, trabecular bone volume measured by μCT in the femurs of CD55KO female mice was increased compared to wild type (WT). Paradoxically, osteoclast number was increased in CD55KO with no differences in osteoblast parameters. Osteoclasts from CD55KO mice exhibited abnormal actin-ring formation and reduced bone-resorbing activity. Moreover, macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL) treatment failed to activate Rac guanosine triphosphatase (GTPase) in CD55KO bone marrow macrophage (BMM) cells. In addition, apoptotic caspases activity was enhanced in CD55KO, which led to the poor survival of mature osteoclasts. Our results imply that CD55KO mice have increased bone mass due to defective osteoclast resorbing activity resulting from reduced Rac activity in osteoclasts. We conclude that CD55 plays an important role in the survival and bone-resorption activity of osteoclasts through regulation of Rac activity. © 2019 American Society for Bone and Mineral Research. Abstract

الإتاحة: https://doi.org/10.1002/jbmr.3861Test
https://academic.oup.com/jbmr/article-pdf/35/1/130/56974643/jbmr3861.pdfTest

المؤلفون: Won, Hee Yeon, Mun, Se Hwan, Shin, Bongjin, Lee, Sun‐Kyeong

المصدر: Arthritis & Rheumatology ; volume 68, issue 5, page 1301-1313 ; ISSN 2326-5191 2326-5205

الوصف: Objective CD97, a member of the 7‐transmembrane epidermal growth factor family of adhesion G protein–coupled receptors, is expressed on various cell types. This study was undertaken to elucidate the functions of CD97 in bone and inflammation in an experimental mouse model, by examining the effect of CD97 on osteoclastogenesis in vitro, characterizing the skeletal phenotype of CD97‐deficient (CD97‐knockout [KO]) mice, and assessing the responses to tumor necrosis factor (TNF) treatment. Methods Femoral tissue and bone marrow (BM)–derived cells from CD97‐KO and wild‐type (WT) mice were assessed using histomorphometric analyses, in vitro cultures, and reverse transcription–polymerase chain reaction. Serum cytokine and chemokine levels in the presence or absence of TNF challenge were analyzed by multiplex assay. Results In cultures of mouse BM‐derived macrophages in vitro, RANKL induced the expression of CD97. In vivo, the trabecular bone volume of the femurs of female CD97‐KO mice was increased, and this was associated with a decrease in the number of osteoclasts. Compared to WT mice, CD97‐KO mice had a reduced potential to form osteoclast‐like cells in vitro. Furthermore, TNF treatment augmented the formation of osteoclasts in the calvaria of CD97‐KO mice in vivo, by increasing the production of RANKL and other cytokines and chemokines and by reducing the production of osteoprotegerin by calvarial cells. Conclusion These findings demonstrate that CD97 is a positive regulator of osteoclast‐like cell differentiation, a mechanism that influences bone homeostasis. However, the presence of CD97 may be essential to suppress the initial osteoclastogenesis that occurs in response to acute and local inflammatory stimuli.

الإتاحة: https://doi.org/10.1002/art.39538Test

المؤلفون: Yu, Jiyeon, Yun, Hyeongseok, Shin, Bongjin, Kim, Yongjin, Park, Eui-Soon, Choi, Seunga, Yu, Jungeun, Amarasekara, Dulshara Sachini, Kim, Sumi, Inoue, Jun-ichiro, Walsh, Matthew C., Choi, Yongwon, Takami, Masamichi, Rho, Jaerang

المساهمون: National Institutes of Health

المصدر: Journal of Biological Chemistry ; volume 291, issue 39, page 20643-20660 ; ISSN 0021-9258

مصطلحات موضوعية: Cell Biology, Molecular Biology, Biochemistry

الإتاحة: https://doi.org/10.1074/jbc.m116.728303Test
https://api.elsevier.com/content/article/PII:S0021925820359342?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0021925820359342?httpAccept=text/plainTest

المؤلفون: Park, Eui-Soon, Choi, Seunga, Shin, Bongjin, Yu, Jungeun, Yu, Jiyeon, Hwang, Jung-Me, Yun, Hyeongseok, Chung, Young-Ho, Choi, Jong-Soon, Choi, Yongwon, Rho, Jaerang

المصدر: Journal of Biological Chemistry ; volume 290, issue 15, page 9660-9673 ; ISSN 0021-9258

مصطلحات موضوعية: Cell Biology, Molecular Biology, Biochemistry

الإتاحة: https://doi.org/10.1074/jbc.m114.609685Test
https://api.elsevier.com/content/article/PII:S0021925820444291?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0021925820444291?httpAccept=text/plainTest

المؤلفون: null Mun, Se Hwan, null Jastrzebski, Sandra, null Kalinowski, Judy, null Zeng, Steven, null Oh, Brian, null Bae, Seyeon, null Eugenia, Giannopoulou, null Khan, Nazir M, null Drissi, Hicham, null Zhou, Ping, null Shin, Bongjin, null Lee, Sun-Kyeong, null Lorenzo, Joseph, null Park-Min, Kyung-Hyun

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc7d3472276b7f59dcc93ea8cdaa3f60Test
https://doi.org/10.1002/jbmr.4270/v4/response1Test

المؤلفون: Hrdlicka, Henry C., Pereira, Renata C., Shin, Bongjin, Yee, Siu-Pok, Deymier, Alix C., Lee, Sun-Kyeong, Delany, Anne M.

المساهمون: National Institutes of Health

المصدر: Bone ; volume 143, page 115779 ; ISSN 8756-3282

مصطلحات موضوعية: Histology, Physiology, Endocrinology, Diabetes and Metabolism

الإتاحة: https://doi.org/10.1016/j.bone.2020.115779Test
https://api.elsevier.com/content/article/PII:S8756328220305676?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S8756328220305676?httpAccept=text/plainTest