更新于：2024-05-01

RORB

RAR related orphan receptor B

更新于：2024-05-01

基本信息

别名

NR1F2、Nuclear receptor ROR-beta、Nuclear receptor RZR-beta

+ [7]

简介

Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated pathway. In cone photoreceptor cells, regulates transcription of OPN1SW. Involved in the regulation of the period length and stability of the circadian rhythm. May control cytoarchitectural patterning of neocortical neurons during development. May act in a dose-dependent manner to regulate barrel formation upon innervation of layer IV neurons by thalamocortical axons. May play a role in the suppression of osteoblastic differentiation through the inhibition of RUNX2 transcriptional activity (By similarity). Isoform 1 is critical for hindlimb motor control and for the differentiation of amacrine and horizontal cells in the retina. Regulates the expression of PTF1A synergistically with FOXN4 (By similarity).

关联

100 项与 RORB 相关的临床结果

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100 项与 RORB 相关的转化医学

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0 项与 RORB 相关的专利（医药）

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149

项与 RORB 相关的文献（医药）

2024-02-01·International journal of molecular sciences

Identification of Novel/Rare EWSR1 Fusion Partners in Undifferentiated Mesenchymal Neoplasms.

Article

作者: Carmen Salguero-Aranda ; Elena Di Blasi ; Lourdes Galán ; Laura Zaldumbide ; Gema Civantos ; David Marcilla ; Enrique de Álava ; Juan Díaz-Martín

Recurrent gene fusions (GFs) in translocated sarcomas are recognized as major oncogenic drivers of the disease, as well as diagnostic markers whose identification is necessary for differential diagnosis. EWSR1 is a 'promiscuous' gene that can fuse with many different partner genes, defining different entities among a broad range of mesenchymal neoplasms. Molecular testing of EWSR1 translocation traditionally relies on FISH assays with break-apart probes, which are unable to identify the fusion partner. Therefore, other ancillary molecular diagnostic modalities are being increasingly adopted for accurate classification of these neoplasms. Herein, we report three cases with rare GFs involving EWSR1 in undifferentiated mesenchymal neoplasms with uncertain differential diagnoses, using targeted RNA-seq and confirming with RT-PCR and Sanger sequencing. Two GFs involved hormone nuclear receptors as 3' partners, NR4A2 and RORB, which have not been previously reported. NR4A2 may functionally replace NR4A3, the usual 3' partner in extraskeletal myxoid chondrosarcoma. The third GF, EWSR1::BEND2, has previously been reported in a subtype of astroblastoma and other rare entities, including a single case of a soft-tissue tumor that we discuss in this work. In conclusion, our findings indicate that the catalogue of mesenchymal neoplasm-bearing EWSR1 fusions continues to grow, underscoring the value of using molecular ancillary techniques with higher diagnostic abilities in the routine clinical setting.

2024-01-23·Neurology

Molecular and Phenotypic Characterization of the RORB-Related Disorder.

Article

作者: Zeynep Gokce-Samar ; Annalisa Vetro ; Julitta De Bellescize ; Tiziana Pisano ; Laloe Monteiro ; Noémie Penaud ; Christian M Korff ; Joel Fluss ; Carla Marini ; Elisabetta Cesaroni ; Blanca Mercedes Alvarez ; Damien Sanlaville ; Nicolas Chatron ; Alexis A Arzimanoglou ; Audrey Labalme ; Vishnu A Cuddapah ; Sarah M Ruggiero ; Francois Lecoquierre ; Gael Nicolas ; Guerrot Anne Marie ; Axel Lebas ; Herve O Testard ; Katherine L Helbig ; Anna Ruiz ; Adeline Ngoh ; Manju A Kurian ; Kimberley Reid ; Robert Spaull ; Pascal Joset ; Georgia Ramantani ; Katharina Steindl ; Martin Krenn ; Lucia Gerstl ; Silvia Vieker ; Dana Craiu ; Manuela Pendziwiat ; Chad Haldeman-Englert ; Ilya Kanivets ; Irina Romanova ; Deepa S Rajan ; Jill A Rosenfeld ; Margaret Au ; Katheryn Grand ; John M ; Arnaud Isapof ; Nathalie Villeneuve ; Thomas Smol ; Roseline Caumes ; Pia Zacher ; Sonja Neuser ; Sigrid Tinschert ; Konrad Platzer ; Tobias Bartolomaeus ; Ines Mohnke ; Maximilian Radtke ; Rami Abou Jamra ; Ingo Helbig ; Floortje E Jansen ; Klaas Koop ; Gabrielle Rudolf ; Sebastien Küry ; Julien Courchet ; Renzo Guerrini ; Gaetan Lesca

BACKGROUND AND OBJECTIVES:

Heterozygous variants in RAR-related orphan receptor B (RORB) have recently been associated with susceptibility to idiopathic generalized epilepsy. However, few reports have been published so far describing pathogenic variants of this gene in patients with epilepsy and intellectual disability (ID). In this study, we aimed to delineate the epilepsy phenotype associated with RORB pathogenic variants and to provide arguments in favor of the pathogenicity of variants.

METHODS:

Through an international collaboration, we analyzed seizure characteristics, EEG data, and genotypes of a cohort of patients with heterozygous variants in RORB. To gain insight into disease mechanisms, we performed ex vivo cortical electroporation in mouse embryos of 5 selected variants, 2 truncating and 3 missense, and evaluated on expression and quantified changes in axonal morphology.

RESULTS:

We identified 35 patients (17 male, median age 10 years, range 2.5-23 years) carrying 32 different heterozygous variants in RORB, including 28 single-nucleotide variants or small insertions/deletions (12 missense, 12 frameshift or nonsense, 2 splice-site variants, and 2 in-frame deletions), and 4 microdeletions; de novo in 18 patients and inherited in 10. Seizures were reported in 31/35 (89%) patients, with a median age at onset of 3 years (range 4 months-12 years). Absence seizures occurred in 25 patients with epilepsy (81%). Nineteen patients experienced a single seizure type: absences, myoclonic absences, or absences with eyelid myoclonia and focal seizures. Nine patients had absence seizures combined with other generalized seizure types. One patient had presented with absences associated with photosensitive occipital seizures. Three other patients had generalized tonic-clonic seizures without absences. ID of variable degree was observed in 85% of the patients. Expression studies in cultured neurons showed shorter axons for the 5 tested variants, both truncating and missense variants, supporting an impaired protein function.

DISCUSSION:

In most patients, the phenotype of the RORB-related disorder associates absence seizures with mild-to-moderate ID. In silico and in vitro evaluation of the variants in our cohort, including axonal morphogenetic experiments in cultured neurons, supports their pathogenicity, showing a hypomorphic effect.

2023-12-28·Biomedicines

Cell-Free Genic Extrachromosomal Circular DNA Profiles of DNase Knockouts Associated with Systemic Lupus Erythematosus and Relation with Common Fragile Sites.

Article

作者: Daniela Gerovska ; Patricia Fernández Moreno ; Aitor Zabala ; Marcos J Araúzo-Bravo

Cell-free extrachromosomal circular DNA (cf-eccDNA) has been proposed as a promising early biomarker for disease diagnosis, progression and drug response. Its established biomarker features are changes in the number and length distribution of cf-eccDNA. Another novel promising biomarker is a set of eccDNA excised from a panel of genes specific to a condition compared to a control. Deficiencies in two endonucleases that specifically target DNA, Dnase1 and Dnase1l3, are associated with systemic lupus erythematosus (SLE). To study the genic eccDNA profiles in the case of their deficiencies, we mapped sequenced eccDNA data from plasma, liver and buffy coat from Dnase1 and Dnase1l3 knockouts (KOs), and wild type controls in mouse. Next, we performed an eccDNA differential analysis between KO and control groups using our DifCir algorithm. We found a specific genic cf-eccDNA fingerprint of the Dnase1l3 group compared to the wild type controls involving 131 genes; 26% of them were associated with human chromosomal fragile sites (CFSs) and with a statistically significant enrichment of CFS-associated genes. We found six genes in common with the genic cf-eccDNA profile of SLE patients with DNASE1L3 deficiency, namely Rorb, Mvb12b, Osbpl10, Fto, Tnik and Arhgap10; all of them were specific and present in all human plasma samples, and none of them were associated with CFSs. A not so distinctive genic cf-eccDNA difference involving only seven genes was observed in the case of the Dnase1 group compared to the wild type. In tissue-liver and buffy coat-we did not detect the same genic eccDNA difference observed in the plasma samples. These results point to a specific role of a set of genic eccDNA in plasma from DNase KOs, as well as a relation with CFS genes, confirming the promise of the genic cf-eccDNA in studying diseases and the need for further research on the relationship between eccDNA and CFSs.

项与 RORB 相关的新闻（医药）

2024-03-31

·今日头条

聚焦特殊人群：老年人和孕妈妈的饮食新知

本期看点：老年人，葫芦巴碱，n-3 PUFA，痴呆症，高脂饮食，孕期饮食，母婴健康，间歇性禁食，肿瘤免疫，信达生物，Ironwood，恒瑞医药，天港医诺，NOOSIO诺希奥该篇日报由R·AI辅助创作生成，人工审核校对。 Nature子刊：NAD+前体葫芦巴碱或可改善老年肌少症 Nature Metabolism——[20.8] ① 线粒体功能失调和NAD+水平低是骨骼肌衰老和肌肉萎缩的特征，本研究发现葫芦巴碱作为NAD+增强剂可通过促进肌肉健康和抑制肌肉老化来治疗年龄相关的肌肉退化；② 在人类中，血清葫芦巴碱水平随着肌肉减少而降低，并与肌肉力量和骨骼肌线粒体氧化磷酸化呈正相关；③ 葫芦巴碱与秀丽隐杆线虫、小鼠和来自健康或肌少症个体的原代肌管中的NAD+结合并增加NAD+水平；④ 葫芦巴碱不会激活GPR109A，而是通过烟酰胺磷酸核糖基转移酶/Preiss-Handler途径在模型中代谢；⑤ 在秀丽隐杆线虫中，葫芦巴碱可以改善线粒体呼吸和生物发生，减少与年龄相关的肌肉萎缩，并通过去乙酰化酶的NAD+依赖机制延长寿命和活动性；⑥ 在雄性小鼠的饮食中补充葫芦巴碱可以增强肌肉力量，防止衰老过程中的疲劳。【原文信息】 Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia 2024-03-19 , doi: 10.1038/s42255-024-00997-x n-3 PUFA或能提升中老年执行功能（荟萃分析） BMC Medicine——[9.3] ① 本研究通过系统回顾和剂量反应荟萃分析，探讨了n-3多不饱和脂肪酸（PUFA）对无痴呆中老年人认知功能的影响，发现n-3 PUFA可能对提升执行功能有益；② 纳入24项研究近一万人，随访3-36个月，在最初的12个月内，每日摄入超过500毫克的n-3 PUFA和最多420毫克的二十碳五烯酸（EPA）可显著提升执行功能；③ 在血液中二十二碳六烯酸（DHA）和EPA水平不是很低的地区，提升执行功能更显著；④ 对于饮食中EPA和DHA水平不是特别低的中老年人群，补充n-3 PUFA可能有助于改善其执行功能。【原文信息】 The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose-response meta-analysis 2024-03-12 , doi: 10.1186/s12916-024-03296-0 健康饮食或通过延缓衰老速率降低痴呆症患病风险 Annals of Neurology——[11.2] ① 健康饮食或与痴呆症风险负相关，但其生物学机制暂未可知，本研究通过纳入Framingham Heart Study阵列中60岁以上1644名无痴呆症老人的随访期间饮食、表观遗传学、血液DNA甲基化及其他数据，将健脑饮食（MIND）定义为健康饮食，分析饮食与痴呆症之间的联系；② 长期遵循MIND饮食的受试者，其生物学衰老速度更慢，且痴呆和全因死亡风险较低；③ 中介分析表明，27%的健康饮食与痴呆症风险的关联是由较慢的生物衰老介导的，而全因死亡率的平行中介比例为57%；④ 排除人口统计学、社会经济、生活方式等因素以及排除基线时认知障碍时，关联数据更具稳健性；⑤ 使用另外2个表观遗传时钟重复分析数据，获得了类似的关联结果。【原文信息】 Diet, Pace of Biological Aging, and Risk of Dementia in the Framingham Heart Study 2024-02-26 , doi: 10.1002/ana.26900 饮食和微量营养素与阿尔茨海默病（综述） Ageing Research Reviews——[13.1] ① 本综述旨在研究营养因素在预防或促进阿尔茨海默病（AD）中认知能力下降中的作用，讨论了地中海饮食、维生素、水果和营养保健品在维持健康认知活动方面的有效积极作用；② AD高风险与西方不均衡饮食有关，这类饮食可诱导皮质醇、儿茶酚胺和血清素水平升高，导致氧化应激、认知能力下降和AD；③ 地中海饮食可以降低AD风险，减少可能增加对AD易感性的脑血管危险因素，并通过改善肠道菌群失调来调节中枢神经系统；④ 某些类型的痴呆在男性中更为常见，但女性患AD的风险更高，可能与女性寿命更长有关；⑤ AD的发病机制与铁、锌和铜等微量营养素的动态变化密切相关。【原文信息】 Impact of micronutrients and nutraceuticals on cognitive function and performance in Alzheimer's disease 2024-01-29 , doi: 10.1016/j.arr.2024.102210 高脂饮食对老年小鼠认知行为和中枢及全身炎症有何影响？ Brain Behavior and Immunity——[15.1] ① 将C57BL/6J幼鼠或老年鼠分别给予标准饮食或高脂饮食，探究高脂饮食对老年或性别差异的小鼠神经炎症、运动以及认知行为的影响；② 高脂饮食会增加小鼠的体重，降低运动活动量，改变焦虑相关的探索行为；③ 高脂饮食会损害年轻雄性空间学习和回忆能力，并影响年轻和老年雄性小鼠的条件性恐惧回忆，但对年轻雌性小鼠的空间学习或恐惧条件反射无影响；④ 高脂饮食会显著影响全身炎症，而对神经炎症的影响有限，尤其是在老年雄性小鼠的海马CA1区域，高脂饮食会加剧微胶质细胞的免疫反应。【原文信息】 Impact of high-fat diet on cognitive behavior and central and systemic inflammation with aging and sex differences in mice 2024-02-24 , doi: 10.1016/j.bbi.2024.02.025 Nature子刊：孕期饮食或可影响宝宝脸型？ Nature Communications——[16.6] ① 在人类胚胎面部组织中，PI3K/AKT/mTORC1/自噬通路的多个成分的转录增强子活性与面部形态相关，这提示该信号通路在人类面部发育中发挥重要作用；② 在小鼠和斑马鱼模型中，抑制mTORC1可轻微改变颅面骨骼的形状，表明mTORC1在调节颅面骨骼发育中起着重要作用；③ 通过改变孕鼠饮食中的蛋白质含量，可调节胚胎mTORC1的活性，进而影响颅面骨骼的发育，提示mTORC1在营养信号调控颅面发育中起着关键作用；④ 本研究揭示了mTORC1信号通路在颅面骨骼发育中的分子机制，为研究环境因素对颅面发育的影响提供了重要线索。【原文信息】 The level of protein in the maternal murine diet modulates the facial appearance of the offspring via mTORC1 signaling 2024-03-26 , doi: 10.1038/s41467-024-46030-3 国内团队Nature子刊：母亲营养过剩如何影响雄性后代下丘脑神经元？ Nature Communications——[16.6] ① 复旦大学的王冠琳和中科院的John R. Speakman团队合作发表文章，通过对母鼠及其后代在低脂和高脂饮食下的代谢特征量化，结合哺乳期高峰时期对后代下丘脑的单核转录组分析，全面解析母体饮食扰动时细胞和分子的变化；② 母体高脂饮食导致雄性后代中包括组胺能（Hdc）、精氨酸加压素/视黄酸受体相关孤儿受体β（Avp/Rorb）和黑皮素相关肽/神经肽Y（AgRP/Npy）在内的神经亚群显著扩张；③ 母体营养过剩时，增加后代中Npy-星形胶质细胞的相互作用；④ 研究绘制了全面的子代下丘脑图谱，并揭示了在发育过程中细胞亚群如何以性别特异性方式对母体膳食脂肪做出反应。【原文信息】 Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice 2024-03-16 , doi: 10.1038/s41467-024-46589-x 孕期益生菌补充对妊娠高血压及相关结果有何影响？ American Journal of Obstetrics & Gynecology MFM——[6.3] ① 通过系统评价和荟萃分析，探讨了孕期服用益生菌对预防子痫前期及相关孕产妇、胎儿和新生儿结果的影响；② 共纳入了29项试验（7735名孕妇），发现益生菌对预防子痫前期（风险比1.14）、早产（风险比0.93）和分娩时孕周（平均差-0.03周）均无显著影响，且这些结果的证据确定性较低；③ 对其他次要结果的影响难以评估，因为相关证据的确定性非常低，未观察到明显的益处或危害；④ 本研究强调了需要更多高质量的试验来明确评估孕期益生菌补充的益处和可能的危害，特别是在营养不良或微生物失调的孕妇中。【原文信息】 The effects of probiotics administration during pregnancy on preeclampsia and associated maternal, fetal and newborn outcomes: a systematic review and meta-analysis 2024-03-04 , doi: 10.1016/j.ajogmf.2024.101322 国内团队：间歇性禁食——改善肥胖新方法（荟萃分析） EClinicalMedicine——[15.1] ① 中国医科大学附属盛京医院赵玉虹、张德宇、吴琪俊和宫婷婷与团队基于糖尿病、超重或肥胖以及代谢综合征三类人群，研究间歇性禁食（IF）与人类健康结果之间的关联，发现间歇性禁食对超重或肥胖成年人的一系列健康结果产生有益影响；② 与超重或肥胖成年人的非干预饮食相比，IF可以降低腰围、脂肪质量、空腹胰岛素、低密度脂蛋白胆固醇、总胆固醇和三酰甘油，但增加了去脂体重；③ 与非干预饮食相比，改良版隔日禁食（MADF）可以降低脂肪质量；④ 在超重或肥胖以及2型糖尿病患者中，IF相对于连续能量限制（CER）饮食可以增加高密度脂蛋白胆固醇水平，但在超重或肥胖中，IF在降低收缩压方面不如CER有效；⑤ 基于敏感性分析，IF干预后体重指数、脂肪量和胰岛素抵抗的稳态模型评估的降低被评定为高质量证据。【原文信息】 Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials 2024-03-11 , doi: 10.1016/j.eclinm.2024.102519 中山大学：膳食限制相关分子活动与肿瘤免疫具有强有力联系！ EBioMedicine——[11.1] ① 中山大学附属第五医院的李曼团队发表文章，在泛癌水平上全面分析饮食限制（DR）相关分子活动在癌症中的作用，揭示了DR相关分子活动与多种癌症类型的肿瘤免疫之间具有强有力的联系，为进一步利用饮食限制相关分子活动改善癌症治疗效果提供参考；② 提出一种计算方法来量化与DR相关的分子活动，通过对27,320个样本中33种癌症类型和30种正常组织的分析，发现DR相关分子活动与肿瘤免疫反应具有紧密的相关性，具有在多种癌症中预测免疫治疗响应性的潜力；③ DR相关分子活动水平较高的患者表现出更好的总生存率和癌症特异性生存率；④ FZD1和G6PD是两个与DR相关的基因，可作为预测肝细胞癌患者预后的生物标志物。【原文信息】 An integrative pan-cancer analysis of the molecular characteristics of dietary restriction in tumour microenvironment 2024-03-19 , doi: 10.1016/j.ebiom.2024.105078 信达生物结肠癌新辅助疗法拟纳入突破性治疗品种 ① 3月29日，国家药监局药品审评中心官网显示，信达生物IBI310和IBI308两款产品拟纳入突破性治疗品种；② 这两款产品联合作为可切除的微卫星高度不稳定型（MSI-H）或错配修复蛋白缺陷型（dMMR）结肠癌的新辅助治疗；③ IBI310是信达生物自研的抗CTLA-4单抗，而信迪利单抗IBI308是与礼来公司合作研发的抗PD-1单抗；④ 早期研究显示，接受IBI310联合信迪利单抗新辅助治疗的患者病理完全缓解率显著，且未增加额外的安全性风险。【原文信息】信达生物抗CTLA-4单抗+抗PD-1单抗拟纳入突破性治疗品种 2024-03-30 , 医药观澜 Ironwood GLP-2疗法2期临床获积极结果 ① 3月29日，Ironwood公司宣布，其研发的Apraglutide在治疗类固醇难治性胃肠道急性移植物抗宿主病（SR GI aGVHD）患者的2期临床试验中，获得积极结果；② Apraglutide是一款长效GLP-2类似物，去年Ironwood公司以超10亿美元从VectivBio公司手中购得；③ 2期临床结果显示，Apraglutide与标准治疗安全性一致，大多数患者在治疗后第28天和第56天产生应答，且应答在第91天得到维持；④ aGVHD是一种罕见的危及生命的疾病，发生在同种异体造血干细胞移植（HSCT）后，通常影响皮肤、胃肠道和肝脏。【原文信息】速递 | 10亿美元收购核心，GLP-2疗法2期临床结果积极 2024-03-29 , 药明康德恒瑞医药ADC新药SHR-A1904获批临床 ① 3月29日，恒瑞医药发布公告称，已收到国家药监局核准签发的关于阿得贝利单抗注射液和注射用SHR-A1904 《药物临床试验批准通知书》；② SHR-A1904是针对Claudin18.2的抗体药物偶联物（ADC），目前在中国、美国、澳大利亚正进行1期临床试验；③ Claudin18.2是一种高特异性的细胞表面分子，在胃癌、胰腺癌、食管癌等瘤种上高表达；④ 阿得贝利单抗注射液已于2023年3月获批上市，用于治疗广泛期小细胞肺癌。【原文信息】恒瑞医药:恒瑞医药关于子公司获得药物临床试验批准通知书的公告 2024-03-29 , 东方财富网天港医诺TGI-5单抗1期临床IND获批 ① 3月22日，合肥天港医诺公司宣布，旗下TGI-5单抗在研管线1期新药临床研究申请（IND），获得国家药监局批准；② TGI-5已于2023年11月30日获得美国FDA临床试验默示许可，国内外尚无同靶点的产品获批上市；③ TGI-5是一种新型免疫检查点单抗药物，拟治疗肝癌、结直肠癌和肺癌等，具有高抗肿瘤活性和良好成药性；④ 天港医诺拥有ABC-NKer技术平台和10余项产品管线，其中半数以上已完成临床前研究，并已完成Pre-A轮融资。【原文信息】天港医诺TGI-5单抗IND获批，成为全球首个同靶点创新药物 2024-03-28 , 触界生物 NOOSIO诺希奥正式进军中国营养膳食市场 ① 近日，美国高端营养品牌NOOSIO诺希奥宣布正式进军中国营养膳食市场；② NOOSIO诺希奥创立于2019年，致力于研发精准匹配各类人群的高品质营养产品；③ 其产品线涵盖了基础营养补充、体重管理、运动恢复、特殊人群营养强化等多个领域，满足现代人多元化健康需求；④ 其产品获美国霍华德休斯医学研究所认证，被推荐为美国麻省总医院的指定用品；⑤ NOOSIO诺希奥将与中国本土科研机构合作，通过线上线下全渠道营销模式服务中国消费者。【原文信息】 NOOSIO营养品牌，正式进军中国营养膳食市场 2024-03-25 , 中华网感谢本期日报的审核者：RZN，Johnson，九卿臣，注册营养师陈彬林，章台柳，Richard，lxx 点击阅读过去10天的日报： 0330 | Akk菌或是免疫性肾病帮凶？Science子刊揭示机制 0329 | 33页综述纵论：超加工食品健康转型的新策略 0328 | Science子刊：锁定肠道中让病毒逃脱免疫的"避风港" 0327 | 10文聚焦菌群-肠-脑轴研究新进展 0326 | 100分综述详解：IBD细胞因子疗法最前沿 0325 | 大肠癌患病为何年轻化？遗传与生活方式的双重影响 0324 | 大型临床试验：补钙补D如何影响老年女性长期健康？ 0323 | Lancet+JAMA领衔，聚焦炎症性肠病诊断与治疗 0322 | 陈豪燕/洪洁等Cell子刊：免疫治疗对老年人更有效，肠道菌群或是隐藏功臣 0321 | 今日Nature双发：促肠癌菌和宿主-菌群互作研究均有新突破

临床结果临床研究

2022-10-14

·World Pharma News

Possible target for treating and preventing osteoarthritis found in little-studied protein

Wear and tear on joints can lead to inflammation, breakdown of cartilage and development of osteoarthritis. Scientists at UF Scripps Biomedical Research have found a possible new target to fight this painful cascade. In a study published Thursday in the journal PLOS One,biochemist Patrick Griffin, Ph.D., and colleague Mi Ra Chang, Ph.D., describe a specific protein that manages activities within chondrocytes, a critical cell type that maintains healthy cartilage in joints. As people age and stress their joints, their chondrocytes begin to fail. The UF Scripps team found that activating a specific protein in these cells called ROR (beta) could restore multiple factors needed for smooth joints to healthier levels, helping to control inflammation. Activating ROR could thus present a useful new strategy to prevent or delay development of the degenerative joint disease osteoarthritis, said Griffin, a professor of molecular medicine and scientific director of UF Scripps Biomedical Research. "People need an osteoarthritis medication that addresses the root cause of cartilage damage and depletion as there currently are no disease-modifying drugs for what is the No. 1 cause of disability in the United States," Griffin said. "While our work is in the early stages, our study suggests that the nuclear receptor ROR could present a novel therapeutic target to protect cartilage damage and perhaps turn on cartilage regeneration." ROR, short for "retinoic acid receptor-related orphan receptor beta," is a type of protein called a nuclear receptor. In our cells, genes switch between periods of activity and inactivity. When nuclear receptors bind to DNA, that activates the cells process of transcribing genes into proteins. ROR has been linked to development of the eyes retina during fetal growth, and it can influence circadian rhythms by controlling clock genes. But its role in maintaining cartilage health was unclear. Griffin has studied causes of bone diseases for many years. He zeroed in on ROR for several reasons. While few studies have been focused on this receptor, some had shown correlation between the receptor's activity and bone loss. So he and Chang set out to better understand it. Chang engineered cell lines to enable the studies. "To our surprise, the gene program upregulated by increase in ROR activity was supportive of the formation of chondrocytes, anti-inflammatory, and protective against cartilage degradation," Chang said. Griffin said the team has launched additional studies because of the enormous need for osteoarthritis solutions. In the United States, an estimated 32 million people live with the painful condition. "This study suggests ROR could be an attractive therapeutic target. However, there's much more we need to unravel," Griffin said. "Specifically, we want to understand more about the mechanism by which ROR impacts chondrocytes and blunts the inflammatory signals that lead to cartilage destruction." Chang MR, Griffin PR. ROR modulates a gene program that is protective against articular cartilage damage. PLoS One. 2022 Oct 13;17(10):e0268663. doi: 10.1371/journal.pone.0268663