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MEF2C regulates osteoclastogenesis and pathologic bone resorption via c-FOS

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Bone Research 2021年第1期9卷 50-62页

作者： Takayuki Fujii Koichi Murata Se-Hwan Mun Seyeon Bae Ye Ji Lee Tannia Pannellini Kyuho Kang David Oliver kyung-hyun park-min Lionel B.Ivashkiv Arthritis and Tissue Degeneration Program and David Z.Rosensweig Genomics Research Center Hospital for Special SurgeryNew YorkNY 10021USA Department of Orthopaedic Surgery Kyoto University Graduate School of MedicineSakyoKyoto 606-8507Japan Department of Advanced Medicine for Rheumatic Diseases Kyoto University Graduate School of MedicineSakyoKyoto 606-8507Japan Department of Biology Chungbuk National UniversityCheongju 28644Republic of Korea BCMB Allied Program Weill Cornell Graduate School of Medical ScienceNew YorkNY 10021USA Immunology and Microbial Pathogenesis Program Weill Cornell Graduate School of Medical ScienceNew YorkNY 10021USA

Osteoporosis is a metabolic bone disease with dysregulated coupling between bone resorption and bone formation,which results in decreased bone mineral *** MEF2C locus,which encodes the transcription factor MADS box transcription enhancer factor 2,polypeptide C(MEF2C),is strongly associated with adult osteoporosis and osteoporotic *** the role of MEF2C in bone and cartilage formation by osteoblasts,osteocytes,and chondrocytes has been studied,the role of MEF2C in osteoclasts,which mediate bone resorption,remains *** this study,we identified MEF2C as a positive regulator of human and mouse osteoclast *** decreased MEF2C expression resulted in diminished osteoclastogenesis,ectopic expression of MEF2C enhanced osteoclast *** transcriptomic and bioinformatic approaches,we found that MEF2C promotes the RANKL-mediated induction of the transcription factors c-FOS and NFATc1,which play a key role in ***,MEF2C binds to FOS regulatory regions to induce c-FOS expression,leading to the activation of NFATC1 and downstream *** deletion of Mef2c in mice resulted in increased bone mass under physiological conditions and protected mice from bone erosion by diminishing osteoclast formation in K/BxN serum induced arthritis,a murine model of inflammatory *** findings reveal direct regulation of osteoclasts by MEF2C,thus adding osteoclasts as a cell type in which altered MEF2C expression or function can contribute to pathological bone remodeling.

关键词： osteoclast MEF2C pathologic

RANKL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts

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Cellular & Molecular Immunology 2023年第1期20卷 94-109页

作者： Seyeon Bae Kibyeong Kim Keunsoo Kang Haemin Kim minjoon Lee Brian Oh Kaichi Kaneko Sungkook Ma Jae Hoon Choi Hojoong Kwak Eun Young Lee Sung Ho park kyung-hyun park-min Arthritis and Tissue Degeneration Program David Z.Rosensweig Genomics Research CenterHospital for Special SurgeryNew YorkNY10021USA Department of Medicine Weill Cornell Medical CollegeNew YorkNY10065USA Department of Biological Science Ulsan National Institute of Science&Technology(UNIST)Ulsan44919Republic of Korea Department of Life Science College of Natural SciencesResearch Institute for Natural SciencesHanyang UniversitySeoulKorea Department of Microbiology Dankook UniversityCheonan3116Republic of Korea Department of Molecular Biology and Genetics Cornell UniversityIthacaUSA Division of Rheumatology Department of Internal MedicineSeoul National University College of MedicineSeoulKorea BCMB Allied Program Weill Cornell Graduate School of Medical SciencesNew YorkNY10021USA

Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANKL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANKL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANKL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANKL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANKL-responsive SEs. The depletion of BATF1/3 inhibited RANKL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. Knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANKL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANKL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to t

关键词： Osteoclasts super-enhancers enhancer RNAs Rheumatoid arthritis

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

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Bone Research 2021年第4期9卷 571-581页

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 Arthritis and Tissue Degeneration Program David Z.Rosensweig Genomics Research CenterNew YorkNYUSA Tissue Engineering Regeneration and RepairHospital for Special SurgeryNew YorkNYUSA Department of Cell and Developmental Biology Weill Cornell Medical CollegeNew YorkNYUSA BCMB allied program Weill Cornell Graduate School of Medical SciencesNew YorkNYUSA Hanyang University Institute for Rheumatology Research SeoulKorea Department of Rheumatology Hanyang University Hospital for Rheumatic DiseasesSeoulKorea Rheumatology College of MedicineKorea UniversitySeoulKorea Department of Medicine Weill Cornell Medical CollegeNew YorkNYUSA

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.

关键词： osteoclast stimulating 1/2

Lactic Acid Fermentation from Coffee Ground Waste Hydrolysate by Lactobacillus rhamnosus

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Journal of Renewable Materials 2019年第4期7卷 365-372页

作者： Ja-Ryong Koo Hye min park Se kyung Kim hyun Shik Yun Department of Biological Engineering Inha UniversityIncheon 22212Korea Institute of Industrial Biotechnology Inha University Research and Business FoundationIncheon 22212Korea

Lactic acid is an important organic acid that is widely used in the food,pharmaceutical,and cosmetic *** acid was produced from coffee ground waste which contains fermentable sugars and is increasingly generated from our daily dietary *** 114 strains of Lactobacillus species,Lactobacillus rhamnosus ATCC 10863 was selected for the production of lactic acid from coffee ground *** alkali pretreatment and saccharification,cellulose and hemicellulose in coffee ground waste were converted into fermentable *** experiments were conducted at various alkali solution,concentrations,and *** pretreatment with 35 g/L of KOH at 121oC for 60 min,the highest concentration of fermentable sugars was *** optimum concentration of Viscozyme L was 2%when saccharification was proceeded at 55oC for 7 *** productivity of lactic acid fermentation was the highest(0.59 g/L/h)at 100 g of coffee ground waste(1x concentration),whereas the lactic acid concentration was the highest at 600 g of coffee ground waste(6x concentration).As the concentration of coffee ground increased,the lactic acid concentration was also increased,however,the amount was not proportional to the coffee ground waste *** this study,it was found that coffee ground waste could be used as a culture medium for Lactobacillus rhamnosus ATCC 10863 through pretreatment and saccharification for the production of lactic acid.

关键词： Coffee ground waste Lactobacillus rhamnosus lactic acid fermentable sugars saccharification alkali pretreatment

Rational strategy for power doubling of monolithic multijunction III-V photovoltaics by accommodating attachable scattering waveguides

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Light(Science & Applications) 2024年第11期13卷 2734-2744页

作者： Shin hyung Lee Hyo Jin Kim Jae-hyun Kim Gwang Yeol park Sun-kyung Kim Sung-min Lee School of Electrical Engineering Korea Advanced Institute of Science and Technology(KAIST)Daejeon 34141Republic of Korea Optoelectronic Convergence Research Center Korea Photonics Technology InstituteGwangju 61007Republic of Korea Department of Applied Physics Kyung Hee UniversityYongin 17104Republic of Korea Department of Electrical Engineering Hanyang UniversitySeoul 04763Republic of Korea Division of Materials Science and Engineering Hanyang UniversitySeoul 04763Republic of Korea

While waveguide-based light concentrators offer significant advantages,their application has not been considered an interesting option for assisting multijunction or other two-terminal tandem solar *** this study,we present a simple yet effective approach to enhancing the output power of transfer-printed multijunction InGaP/GaAs solar *** utilizing a simply combinable waveguide concentrator featuring a coplanar waveguide with BaSO4 Mie scattering elements,we enable the simultaneous absorption of directly illuminated solar flux and indirectly waveguided *** deployment of cells is optimized for front-surface photon collection in monofacial *** systematic comparisons across various waveguide parameters,supported by both experimental and theoretical quantifications,we demonstrate a remarkable improvement in the maximum output power of a 26%-efficient cell,achieving an enhancement of~93%with the integration of the optimal scattering ***,a series of supplementary tests are conducted to explore the effective waveguide size,validate enhancements in arrayed cell module performance,and assess the drawbacks associated with rear *** findings provide a comprehensive understanding of our proposed approach towards advancing multi-junction photovoltaics.

关键词： waveguide scattering power

Three-dimensional label-free morphology of CD8+T cells as a sepsis biomarker

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Light(Science & Applications) 2023年第12期12卷 2565-2576页

作者： minDong Sung Jong hyun Kim hyun-Seok min Sooyoung Jang JaeSeong Hong Bo Kyu Choi JuHye Shin kyung Soo Chung Yu Rang park Division of Pulmonary and Critical Care Medicine Department of Internal MedicineYonsei University College of MedicineSeoulRepublic of Korea Department of Biomedical Systems Informatics Yonsei University College of MedicineSeoulRepublic of Korea Tomocube Inc155 Sinseong-roShinsung-dongYuseong-guDaejeonRepublic of Korea

Sepsis is a dysregulated immune response to infection that leads to organ dysfunction and is associated with a high incidence and mortality *** lack of reliable biomarkers for diagnosing and prognosis of sepsis is a major challenge in its *** aimed to investigate the potential of three-dimensional label-free CD8+T cell morphology as a biomarker for *** study included three-time points in the sepsis recovery cohort(N=8)and healthy controls(N=20).Morphological features and spatial distribution within cells were compared among the patients'*** developed a deep learning model to predict the diagnosis and prognosis of sepsis using the internal cell *** between the morphological features and clinical indices were *** morphological features and spatial distribution differed significantly between patients with sepsis and healthy controls and between the survival and non-survival *** model for predicting the diagnosis and prognosis of sepsis showed an area under the receiver operating characteristic curve of nearly 100%with only a few cells,and a strong correlation between the morphological features and clinical indices was *** study highlights the potential of three-dimensional label-free CD8+T cell morphology as a promising biomarker for *** approach is rapid,requires a minimum amount of blood samples,and has the potential to provide valuable information for the early diagnosis and prognosis of sepsis.

关键词： sepsis diagnosis Morphological

Comparison of the efficacy and safety of once-daily dosing and on-demand use of udenafil for type 2 diabetic patients with erectile dysfunction

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Asian Journal of Andrology 2015年第1期17卷 143-148,I0011,I0012页

作者： Soon hyun park Sung Woo park Bong Yun Cha Ie Byung park kyung Wan min Yeon Ah Sung Tae Hwa Kim Jae min Lee Kang Seo park Department of Internal Medicine Eulji University School of Medicine Daejeon 302-799 South Korea Department of Endocrinology and Metabolism Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine Seou1110-746 South Korea Department of Endocrinology and Metabolism College of Medicine the Catholic University of Korea Seou1137-701 South Korea Department of Internal Medicine Gachon University of Medicine and Science Graduate School of Medicine Incheon 405-760 South Korea Department of Internal Medicine Eulji University School of Medicine Seou1139-872 South Korea Department of Endocrinology Ewha Woman's University School of Medicine Seoul 158-710 South Korea Department of Internal Medicine College of Medicine Hanyang University Seoul 133-792 South Korea.

We compared the efficacy and safety between once-daily dosing and on-demand use of udenafil for type 2 diabetic patients with erectile dysfunction （ED）. A multi-center, randomized, open-label, parallel-group, 12-week study was conducted. 161 patients who improved with on-demand 200 mg of udenafil according to Sexual Encounter Profile （SEP） diary Question 2 and 3 （Q2 and Q3） were randomized into 200 mg on-demand （n = 80） or 50 mg once-daily （n = 81） dosing groups for 8 weeks. The dosing period was followed by a 4-week treatment-free period. The primary efficacy endpoint was the change of the International Index of Erectile Function （IIEF） erectile function domain （EFD） score. The secondary efficacy endpoints included changes to the SEP diary Q2, Q3, IIEF Q3, Q4, other domains of IIEF, Global Assessment Question, and shift to the normal rate （EFD 〉 26）. Vascular endothelial markers were also assessed. The IIEF-EFD score of both groups improved after 8 weeks of treatment （P 〈 0.0001）. There was no statistically significant difference between two groups. Improvement was not maintained after the treatment-free follow-up period. Similar results were observed in the secondary efficacy endpoints. There was also no significant difference in vascular endothelial markers. Daily udenafil was well-tolerated, and there was no significant difference in the adverse drug reactions and adverse events between the two groups. Flushing and headache were the most frequent adverse events. Both regimens improved ED in diabetic patients and were well-tolerated. Further studies are needed to assess the effect of daily udenafil treatment in diabetic patients.

关键词： erectile dysfunction International Index of Erectile Function once-daily dosing ptiosphodiesterase type 5 inhibitor type 2 diabetes mellitus udenafil

Multi-faceted small molecule for Alzheimer’s disease

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Neural Regeneration Research 2023年第10期18卷 2198-2199页

作者： min Hee park Hee kyung Jin Jae-sung Bae KNU Alzheimer’s Disease Research Institute Department of PhysiologySchool of MedicineKyungpook National UniversityDaeguSouth Korea KNU Alzheimer’s Disease Research Institute Department of Laboratory Animal MedicineCollege of Veterinary MedicineKyungpook National UniversityDaeguSouth Korea

The main pathologies of Alzheimer’s disease(AD)are the accumulation of amyloid-B(AB)and tau ta ngles,and these two fundamental pathologies accompany the va rious neuropathological features,such as neuroinfla mmation,... 详细信息

关键词： Alzheimer tau amyloid

Exercise-induced muscle fatigue in the unaffected knee joint and its influence on postural control and lower limb kinematics in stroke patients

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Neural Regeneration Research 2017年第5期12卷 765-769页

作者： Sun Wook park Sung min Son Na kyung Lee Department of Physical Therapy Faculty of Health Science Eulji University Department of Physical Therapy College of Health Science Cheongju University Department of Physical Therapy College of Rehabilitation Science Daegu University

This study aimed to investigate the effects of exercise-induced muscle fatigue in the unaffected knee joint on postural control and kinematic changes in stroke patients. Forty participants（20 stroke patients, 20 age-matched healthy participants） were recruited. To induce fatigue, maximum voluntary isometric contractions were performed in the unaffected knee joint in a Leg Extension Rehab exercise machine using the pneumatic resistance. We measured static and dynamic balance and lower-limb kinematics during gait. Changes in postural control parameters anteroposterior sway speed and total center of pressure distance differed significantly between the stroke and control groups. In addition, changes in gait kinematic parameters knee and ankle angles of initial contact differed significantly between stroke（paretic and non-paretic） and control groups. Muscle fatigue in the unaffected knee and ankle impaired postural control and debilitates kinematic movement of ipsilateral and contralateral lower limbs, and may place the fatigued stroke patients at greater risk for falls.

关键词： nerve regeneration knee muscle fatigue stroke postural control gait kinemetics neural regeneration