更新于：2024-11-01

OSCAR

更新于：2024-11-01

基本信息

别名

hOSCAR、OSCAR、osteoclast associated Ig-like receptor

+ [6]

简介

Regulator of osteoclastogenesis which plays an important bone-specific function in osteoclast differentiation.

关联

项与 OSCAR 相关的药物

WO2022119076

专利挖掘

靶点

GLP-1R x OSCAR

作用机制-

在研机构

Immunoforge Co. Ltd.初创企业

原研机构

Immunoforge Co. Ltd.初创企业

在研适应症

皮肤和肌肉骨骼疾病

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

WO2023173091

专利挖掘

靶点

OSCAR

作用机制-

在研机构

NGM Biopharmaceuticals, Inc.

原研机构

NGM Biopharmaceuticals, Inc.

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

HG-1321

靶点

OSCAR

作用机制

OSCAR modulators

在研机构-

原研机构

Human Genome Sciences, Inc.

在研适应症-

非在研适应症

骨病 [+2]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 OSCAR 相关的临床结果

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100 项与 OSCAR 相关的转化医学

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0 项与 OSCAR 相关的专利（医药）

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286

项与 OSCAR 相关的文献（医药）

2024-09-02·PNAS Nexus

Cell-based assays and comparative genomics revealed the conserved and hidden effects of Wolbachia on insect sex determination

Article

作者: Sasaki, Tetsuhiko ; Arai, Hiroshi ; Herran, Benjamin ; Kageyama, Daisuke ; Miyata, Mai ; Sugimoto, Takafumi N

AbstractIt is advantageous for maternally transmitted endosymbionts to skew the sex ratio of their hosts toward females. Some endosymbiotic bacteria, such as Wolbachia, cause their insect hosts to exclusively produce female offspring through male killing (MK) or feminization. In some lepidopteran insects, MK is achieved by affecting the sex-determining process in males, and a unique mechanism of MK and its functional link with feminization have been implicated. However, comparative analysis of these phenotypes is often difficult because they have been analyzed in different host–symbiont systems, and transinfection of Wolbachia across different hosts is often challenging. In this study, we demonstrated the effects of nine Wolbachia strains on the splicing of sex-determining genes in Lepidoptera by fixing the host genetic background using a cell culture system. Cell transinfection assays confirmed that three MK-inducing Wolbachia strains and one feminization-inducing Wolbachia strain increased the female-type splicing products of the core sex-determining genes doublesex, masculinizer, and zinc finger protein 2. Regarding Wolbachia strains that do not induce MK/feminization, three had no effect on these sex-determining genes, whereas two strains induced female-type splicing of masculinizer and doublesex but not zinc finger protein 2. Comparative genomics confirmed that homologs of oscar, the Wolbachia gene responsible for MK in Ostrinia, were encoded by four MK/feminizing Wolbachia strains, but not by five non-MK/nonfeminizing strains. These results support the conserved effects underlying MK and feminization induced by oscar-bearing Wolbachia and suggested other potential mechanisms that Wolbachia might employ to manipulate host sex.

2024-05-01·Virchows Archiv

Gastroblastoma with a novel ACTB::GLI1 gene fusion in a 19-year-old male

Article

作者: Shabbir, Junaid ; Ligato, Saverio ; Schipper, Bret ; Glomski, Krzysztof ; Earle, Jonathan ; Mnayer, Laila

Gastroblastoma is a rare gastric biphasic tumor composed of mesenchymal and epithelial elements in variable proportions. These tumors usually arise in the gastric antrum of children and young adults and are reported to harbor a recurrent MALAT1::GLI1 fusion. Herein we report a case of gastroblastoma in a 19-year-old male who presented with intermittent epigastric abdominal discomfort. Antrectomy revealed a 5.6-cm multi-lobulated, tan-pink mass with solid and focally cystic areas involving the submucosa, muscularis propria, and subserosa. All tumor cells demonstrated immunoreactivity for GLI-1, CD56, and vimentin; epithelial elements expressed pancytokeratins (AE1/AE3 and Oscar), and mesenchymal cells demonstrated focal positivity for CD10. Next generation sequencing revealed a novel ACTB::GLI1 fusion without evidence of the recurrent MALAT1::GLI1 fusion. Nine months after surgery, the patient is well without evidence of recurrence or metastases. To our knowledge, this is the first case of gastroblastoma harboring this novel ACTB::GLI1 fusion.

2024-02-01·Free Radical Biology and Medicine

Sestrin2 inhibits RANKL-induced osteoclastogenesis through AMPK activation and ROS inhibition

Article

作者: Kim, Inyoung ; Kim, Nacksung ; Kim, Jung Ha ; Seong, Semun ; Kim, Kabsun ; Koh, Jeong-Tae

Sestrins are stress-responsive proteins with antioxidant properties. They participate in cellular redox balance and protect against oxidative damage. This study investigated the effects of Sestrin2 (Sesn2) on osteoclast differentiation and function. Overexpressing Sesn2 in osteoclast precursor cells significantly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis. This was assessed as reduced expression of various osteoclast markers, including c-Fos, nuclear factor of activated T cells 1 (NFATc1), osteoclast-associated receptor, tartrate-resistant acid phosphatase, and cathepsin K. Conversely, downregulation of Sesn2 produced the opposite effect. Mechanistically, Sesn2 overexpression enhanced AMPK activation and the nuclear translocation of nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2), promoting antioxidant enzymes. Moreover, azithromycin (Azm) induced Sesn2 expression, which suppressed RANKL-induced osteoclast differentiation. Specifically, Azm treatment reduced RANKL-induced production of reactive oxygen species in osteoclasts. Furthermore, intraperitoneal administration of Azm ameliorated RANKL-induced bone loss by reducing osteoclast activity in mice. Taken together, our results suggested that Azm-induced Sesn2 act as a negative regulator of RANKL-induced osteoclast differentiation through the AMPK/NFATc1 signaling pathway. Concisely, targeting Sesn2 can be a potential pharmacological intervention in osteoporosis.