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Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

Bone Research 2024年第1期12卷 180-198页

作者： Morten s.Hansen Kaja Madsen Maria Price kent søe Yasunori Omata Mario M.Zaiss Caroline M.Gorvin Morten Frost Alexander Rauch Molecular endocrinology Laboratory(KMeB) Department of EndocrinologyOdense University HospitalDK-5000 Odense CDenmark Department of Clinical Research Faculty of Health SciencesUniversity of Southern DenmarkDK-5000 Odense CDenmark Clinical Cell Biology Pathology Research UnitDepartment of Clinical ResearchUniversity of Southern DenmarkDK-5000 Odense CDenmark Institute of Metabolism and systems Research(IMsR)and Centre for Diabetes Endocrinology and Metabolism(CEDAM)University of BirminghamBirmingham B152TTUK Centre for Membrane Proteins and Receptors(COMPARe) Universities of Birmingham and NottinghamBirmingham B152TTUK Department of Molecular Medicine University of Southern DenmarkDK-5000 Odense CDenmark Department of Orthopedic surgery Faculty of MedicineThe University of TokyoTokyo 113-8655Japan Department of Internal Medicine 3 Rheumatology and ImmunologyFriedrich-Alexander-University Erlangen-Nürnberg(FAU)and Universitätsklinikum ErlangenD-91054 ErlangenGermany Deutsches Zentrum Immuntherapie(DZI) Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum ErlangenD-91054 ErlangenGermany steno Diabetes Center Odense Odense University HospitalDK-5000 Odense CDenmark

enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone *** novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment *** study aimed to provide an overview of transcriptional reprogramming during human osteoclast *** were differentiated from CD14+monocytes from eight female *** sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across *** patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density *** analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional *** donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature *** expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density sNPs,suggesting that they play a pivotal role in osteoclast differentiation and *** regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(ssTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating ssTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature *** conclus

关键词： osteoclast programming identif

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Pit-and trench-forming osteoclasts:a distinction that matters

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Bone Research 2015年第4期3卷 199-209页

作者： Ditte MH Merrild Dinisha C Pirapaharan Christina M Andreasen Per Kjxrsgaard-Andersen Anas MJ Mùller Ming Ding Jean-Marie Delaissé kent sùe Department of Clinical Cell Biology Vejle Hospital/Lillebaelt HospitalInstitute of Regional Health ResearchUniversity of Southern Denmark Orthopaedic Research Laboratory Department of Orthopedic Surgery and TraumatologyOdense University HospitalUniversity of Southern Denmark Department of Orthopedic surgery Vejle Hospital/Lillebaelt Hospital

Osteoclasts（OCs）seeded on bone slices either drill round pits or dig long *** pits correspond to intermittent resorption,trenches correspond to continuous and faster resorption and require a distinct assembly of the resorption *** is unknown whether the distinction between pits and trenches has any biological *** OCs prepared from different blood donors,we found that female OCs achieved increased resorption mainly through pit formation,whereas male OCs did so through trench *** formation went along with high collagenolytic activity and high cathepsin K（CatK）expression,thereby allowing deeper demineralization.A specific CatK inhibitor abrogated the generation of trenches,while still allowing the generation of *** obtained from bone marrow were more prone to generate trenches than those obtained from *** electron microscopy of bone surfaces eroded in vivo showed trenches and pits of similar size as those made by OCs in *** conclude that the distinction between trench-and pit-forming OCs is relevant to the differences among OCs from different skeletal sites,different individuals,including gender,and results from differences in colIagenolytic *** indicates a biological relevance and highlights the importance of discriminating between pits and trenches when assessing resorption.

关键词： trench cathepsin collagen faster prone assembly highlights thereby correspond apparatus

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Aging and menopause reprogram osteoclast precursors for aggressive bone resorption

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Bone Research 2020年第3期8卷 333-342页

作者： Anais Marie Julie Moller Jean-Marie Delaisse Jacob Bastholm Olesen Jonna skov Madsen Luisa Matos Canto Troels Bechmann silvia Regina Rogatto kent soe Clinical Cell Biology Lillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark Department of Regional Health Research University of Southern Denmark5230 Odense MDenmark Department of Clinical Biochemistry and Immunology Lillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark Clinical Cell Biology Department of PathologyOdense University Hospital5000 Odense CDenmark Department of Clinical Research University of Southern Denmark5230 Odense MDenmark Department of Molecular Medicine University of Southern Denmark5230 Odense MDenmark Department of Clinical Genetics Lillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark Department of Oncology Lillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark OPeN Odense Patient data Explorative NetworkOdense University Hospital5000 Odense CDenmark

Women gradually lose bone from the age of〜35 years,but around menopause,the rate of bone loss escalates due to increasing bone resorption and decreasing bone formation levels,rendering these individuals more prone to developing *** increased osteoclast activity has been linked to a reduced estrogen level and other hormonal ***,it is unclear whether intrinsic changes in osteoclast precursors around menopause can also explain the increased osteoclast ***,we set up a protocol in which CD14f blood monocytes were isolated from 49 female donors(40-66 years old).Cells were differentiated into osteoclasts,and data on differentiation and resorption activity were *** multiple linear regression analyses combining in vitro and in vivo data,we found the following:(1)age and menopausal status correlate with aggressive osteoclastic bone resorption in vitro;(2)the type I procollagen N-terminal propeptide level in vivo inversely correlates with osteoclast resorption activity in vitro;(3)the protein level of mature cathepsin K in osteoclasts in vitro increases with age and menopause;and(4)the promoter of the gene encoding the dendritic cell-specific transmembrane protein is less methylated with *** conclude that monocytes are"reprogrammed"in vivo,allowing them to"remember"age,the menopausal status,and the bone formation status in vitro,resulting in more aggressive *** discovery suggests that this may be mediated through DNA *** suggest that this may have clinical implications and could contribute to understanding individual differences in age-and menopause-induced bone loss.

关键词： osteoclast menopause osteoporosis

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engineering a non-model yeast Rhodotorula mucilaginosa for terpenoids synthesis

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synthetic and systems Biotechnology 2024年第3期9卷 569-576页

作者： Qiongqiong Chen Liting Lyu Haizhao Xue Aabid Manzoor shah Zongbao kent Zhao Laboratory of Biotechnology Dalian Institute of Chemical PhysicsCAS457 Zhongshan RoadDalian116023China MOe Key Laboratory of Bio-Intelligent Manufacturing School of BioengineeringDalian University of TechnologyDalian116024China University of Chinese Academy of sciences 19 Yuquan RoadBeijing100049China

Terpenoids have tremendous biological activities and are widely employed in food,healthcare and pharmaceutical *** synthetic biology to product terpenoids from microbial cell factories presents a promising alternative route compared to conventional methods such as chemical synthesis or *** red yeast Rhodotorula mucilaginosa has been widely studied due to its natural production capacity of carotenoid and lipids,indicating a strong endogenous isoprene pathway with readily available metabolic *** study constructed several engineered strains of *** with the aim of producing different ***α-terpineol was produced by expressing theα-terpineol synthase from Vitis *** titer ofα-terpineol was further enhanced to 0.39 mg/L by overexpressing the endogenous rate-limiting gene of the MVA *** ofα-farnesene synthase from Malus domestica,in combination with MVA pathway rate-limiting gene resulted in significant increase inα-farnesene production,reaching a titer of 822 mg/*** carotenoid degradation productβ-ionone was produced at a titer of 0.87 mg/L by expressing theβ-ionone synthase from Petunia *** study demonstrates the potential of *** as a platform host for the direct biosynthesis of various terpenoids and provides insights for further development of such platforms.

关键词： Rhodotorula mucilaginosa synthetic biology α-Terpineol β-Ionone α-Farnesene

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Molecularly engineered lignin to polyphenol via organocatalysis as an active sunscreen ingredient

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Journal of Bioresources and Bioproducts 2024年第2期9卷 197-210页

作者： Yuanlong Guo Pengcheng Liu Lei Deng Changwei Lui Michael North Gang Hu Qitian Huang Zongbao kent Zhao Haibo Xie Department of Polymeric Materials&engineering Guizhou UniversityGuiyang 550025China KZJ New Materials Group Guizhou Co.Ltd. Guizhou 551200China Green Chemistry Centre of excellence Department of ChemistryUniversity of YorkYork YO105DDUK Dalian Institute of Chemical Physics Chinese Academy of SciencesDalian 116023China

Phenolation is one of the effective strategies to synthesize lignin-based polyphenols,improve lignin’s properties,and extend its value-added applications in biological,medicinal and cosmetic ***,by taking the structural feature advantage of lignin,an effective and green strategy was developed to molecularly engineer lignin into a robust lignin-3-(2-hydroxyphenyl)propionate ester(LPPe)derivative via a transesterification reaction between 3,4-dihydrocoumarin(DHC)and the aliphatic hydroxyls in lignin under *** strategy is optimized and the novel derivative was systematically characterized by ^(1)H,^(13)C and ^(31)P nuclear magnetic resonance(NMR)and Fourier transform infrared(FT-IR)*** findings indicated that the successful introduction of 3-(2-hydroxyphenyl)propionate groups using a OH groups/DHC/organic base mo-lar ratio of 1꞉1꞉0.3 at 120℃ for 6 h increased the content of phenolic hydroxyl groups from 1.7931 to 3.0179 mmol/g,and the LPPe exhibited excellent ultraviolet-absorbing and antioxidant per-formance with up to 90%free radical scavenging activity within 20 min using 5 mg/mL of *** addition,good biocompatibility and a high sun protection factor(sPF)value of 40.9 were achieved at 5%(w)dosage of LPPe in the cream,indicating its significant application potential in sunscreen.

关键词： Phenolation of lignin Organocatalysis 3,4-dihydrocoumarin Antioxidant sunscreen cream

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elucidating regulatory processes of intense physical activity by multi-omics analysis

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Military Medical Research 2024年第4期11卷 479-499页

作者： ernesto s.Nakayasu Marina A.Gritsenko Young-Mo Kim Jennifer e.Kyle Kelly G.stratton Carrie D.Nicora Nathalie Munoz Kathleen M.Navarro Daniel Claborne Yuqian Gao Karl K.Weitz Vanessa L.Paurus kent J.Bloodsworth Kelsey A.Allen Lisa M.Bramer Fernando Montes Kathleen A.Clark Grant Tietje Justin Teeguarden Kristin e.Burnum-Johnson Biological sciences Division Pacific Northwest National LaboratoryRichlandWA 99352USA environmental and Molecular sciences Division Pacific Northwest National LaboratoryRichlandWA 99352USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthWestern States DivisionDenverCO 80204USA Computational Analytics Division Pacific Northwest National LaboratoryRichlandWA 99352USA National security Directorate Pacific Northwest National LaboratoryRichlandWA 99352USA Los Angeles County Fire Department Los AngelesCA 90063USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthRespiratory Health DivisionMorgantownWV 26505USA environmental and Molecular Toxicology Oregon State UniversityCorvallisOR 97331USA

Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,military,and sports.A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work ***:To study regulatory processes in intense physical activity simulating real-life conditions,we performed a multi-omics analysis of 3 biofluids(blood plasma,urine,and saliva)collected from 11 wildland firefighters before and after a 45 min,intense exercise *** profiles ***-exercise were compared by student’s t-test followed by pathway analysis and comparison between the different omics ***:Our multi-omics analysis identified and quantified 3835 proteins,730 lipids and 182 metabolites combining the 3 different types of *** blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy *** urine analysis showed a strong,concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites,reabsorption of nutrients and maintenance of fluid *** saliva,we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides.A systematic literature review identified 6 papers that support an altered susceptibility to respiratory ***:This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility,suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

关键词： Multi-omics analysis Intense exercise Human performance Biofluids Metabolism Immunity

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小拜登离席

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财新周刊 2024年第3期 12-13页

作者： kent Nishimura(图) 无不详视觉中国

当地时间2024年1月10日,美国首部华盛顿,美国总统拜登的儿子亨特·拜登(中)在国会听证会上露面,当时众议院共和党人正准备提出决议定其藐视国会,亨特一行人突然离场。当日,经过6小时的听证会后,委员会23名成员投票支持该决议、14名成员... 详细信息

当地时间2024年1月10日,美国首部华盛顿,美国总统拜登的儿子亨特·拜登(中)在国会听证会上露面,当时众议院共和党人正准备提出决议定其藐视国会,亨特一行人突然离场。当日,经过6小时的听证会后,委员会23名成员投票支持该决议、14名成员反对。众议院将就此事进行全体投票,并可能对亨特·拜登提出进一步的刑事诉讼。

关键词：众议院共和党人听证会刑事诉讼国会亨特投票决议

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Predictability of Us tornado outbreak seasons using eNsO and northern hemisphere geopotential height variability

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Geoscience Frontiers 2016年第1期7卷 21-31页

作者： kent H.sparrow Andrew e.Mercer Department of Geosciences Mississippi State University

The predictability of dangerous atmospheric phenomena such as tornado outbreaks has generally been limited to a week or less. However, recent work has demonstrated the importance of the Rossby wavetrain phasing over the United states in establishing outbreak-favorable environments. The predictability of Rossby wavetrain phasing is strongly related to numerous climate-scale interannual variability indices, which are predictable many months in advance. To formalize the relationship between interannual variability indices and seasonal tornado outbreak frequency, indices derived from monthly mean Northern Hemisphere 500-hPa and 1000-hPa geopotential height fields and Ni？o 3.4 indices for eNsO phase were compared to annual tornado outbreak seasonal frequencies. statistical models predicting seasonal outbreak frequency were established using linear（stepwise multivariate linear regressione sMLR） and nonlinear（support vector regressione sVR） statistical modeling *** stepwise methodology revealed predictors that are important in establishing outbreak-favorable environments at long lead times. Additionally, the results of the statistical modeling revealed that the nonlinear sVR technique reduced root mean square errors produced by the control sMLR technique by 28% and provided more consistent forecasts. A preliminary physical analysis revealed that years with high outbreak frequencies were associated with the presence of 500-mb troughs over the central and western Us during the peak of outbreak season, while lower frequencies were consistent with ridging over the Us or northwest flow over the Plains. These patterns support the results of the statistical modeling, which demonstrate the utility of geopotential height variability as a predictability measure of outbreak frequency.

关键词： Interannual variability support vector regression Climate predictability Tornado outbreaks

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sYNGR4 and PLeKHB1 deregulation in motor neurons of amyotrophic lateral sclerosis models: potential contributions to pathobiology

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Neural Regeneration Research 2022年第2期17卷 266-270页

作者： Rita F.Marques kent e.Duncan Institute for Biochemistry and Molecular Biology Department of ChemistryUniversity of HamburgHamburgGermany Neuronal Translational Control Research Group Center for Molecular Neurobiology Hamburg(ZMNH)University Medical Center Hamburg-EppendorfHamburgGermany

Amyotrophic lateral sclerosis is the most common adult-onset neurodegenerative disease affecting motor neurons. Its defining feature is progressive loss of motor neuron function in the cortex, brainstem, and spinal cord, leading to paralysis and death. Despite major advances in identifying genes that can cause disease when mutated and model the disease in animals and cellular models, it still remains unclear why motor symptoms suddenly appear after a long pre-symptomatic phase of apparently normal function. One hypothesis is that age-related deregulation of specific proteins within key cell types, especially motor neurons themselves, initiates disease symptom appearance and may also drive progressive degeneration. Genome-wide in vivo cell-type-specific screening tools are enabling identification of candidates for such proteins. In this minireview, we first briefly discuss the methodology used in a recent study that applied a motor neuron-specific RNAseq screening approach to a standard model of TAR DNA-binding protein-43(TDP-43)-driven amyotrophic lateral sclerosis. A key finding of this study is that synaptogyrin-4 and pleckstrin homology domain-containing family B member 1 are also deregulated at the protein level within motor neurons of two unrelated mouse models of mutant TDP-43 driven amyotrophic lateral sclerosis. Guided by what is known about molecular and cellular functions of these proteins and their orthologs, we outline here specific hypotheses for how changes in their levels might potentially alter cellular physiology of motor neurons and detrimentally affect motor neuron function. Where possible, we also discuss how this information could potentially be used in a translational context to develop new therapeutic strategies for this currently incurable, devastating disease.

关键词： amyotrophic lateral sclerosis glucagon-like peptide-1 receptor motor neuron disease mouse model neurodegeneration phosphatidylserine pleckstrin homology domain synaptogyrin TAR DNA-binding protein-43 vesicle transport

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In the presence of danger: the extracellular matrix defensive response to central nervous system injury

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Neural Regeneration Research 2014年第4期9卷 377-384页

作者： Lyn B.Jakeman kent e.Williams Bryan Brautigam Department of Physiology and Cell Biology Ohio State University Wexner Medical CenterColumbusOHUSA Neuroscience Graduate studies Program Ohio State University Wexner Medical CenterColumbusOHUSA Biomedical Research Graduate Program Ohio State University Wexner Medical CenterColumbusOHUSA OsU Center for Brain and spinal Cord Repair Ohio State University Wexner Medical CenterColumbusOHUSA

Glial cells in the central nervous system （CNs） contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient on and axon potential propagation. In the normal adult CNs, the extracellular matrix （eCM） is relatively stable except in selected regions characterized by dynamic remodeling. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter becomes a focus of acute neuroinflammation. The activation of the surrounding glial cells leads to a dramatic change in the composition of the eCM at the edges of the lesion, creating a perilesion environment dominated by growth inhibitory molecules and restoration of the peripheral/ central nervous system border. An advantage of this response is to limit the invasion of damaging cells and diffusion of toxic molecules into the spared tissue regions, but this occurs at the cost of inhibiting migration of endogenous repair cells and preventing axonal regrowth. The following review was prepared by reading and discussing over 200 research articles in the field published in PubMed and selecting those with significant impact and/or controversial points. This article highlights structural and functional features of the normal adult CNs eCM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury. Current research strategies directed at modifying the inhibitory perilesion microenvironment without eliminating the protective functions of glial cell activation are discussed.

关键词： nerve regeneration glial scar proteoglycan axon growth spinal cord injury contusion inhibitory inflammation astrocyte macrophage neural regeneration

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