XLαs通过影响线粒体功能调控颅骨发育的研究  

Regulatory Effects of XLαs on Cranial Bone Development through Influencing Mitochondrial Function

作　　者：左祎怡 何青 ZUO Yiyi;HE Qing(State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Wuhan University,Wuhan 430079,China)

机构地区：[1]口颌系统重建与再生全国重点实验室,口腔生物医学教育部重点实验室,口腔医学湖北省重点实验室,武汉大学口腔医(学)院,湖北武汉430079

出　　处：《口腔医学研究》2024年第7期587-592,共6页Journal of Oral Science Research

基　　金：国家自然科学基金(编号:82072483)。

摘　　要：目的:本研究旨在探究超大型刺激性G蛋白α亚单位(extra-large stimulatory G protein alpha subunit, XLαs)在小鼠颅骨发育和成骨分化中的功能及分子机制。方法:通过构建XLαs第一外显子敲除的小鼠模型,运用阿尔新蓝茜素红染色技术分析颅骨表型变化。从小鼠颅骨中分离原代颅骨成骨细胞,进行体外培养并诱导成骨分化,同时通过实时荧光定量聚合酶链反应和RNA测序技术对基因表达及其功能进行分析。结果:实验结果显示,XLαs敲除小鼠颅缝宽度增加(P<0.05),颅骨未矿化区域明显增多(P<0.001),且成骨分化能力受抑制(P<0.01)。RNA测序进一步揭示XLαs缺失影响了线粒体功能。结论:本研究证实了XLαs在调节颅骨发育和成骨分化中的关键作用,特别是通过影响线粒体功能来发挥其调控效应。这一发现为针对GNAS突变导致的颅骨发育异常提供了新的治疗策略,具有潜在的临床应用价值。Objective:To investigate the role and underlying molecular mechanism of extra-large stimulatory G protein alpha subunit(XLαs)in cranial bone development.Methods:Utilizing a genetically engineered mouse model lacking the specific exon 1 of XLαs,cranial morphology were analyzed through alician blue and alizarin red staining.Primary cranial osteoblasts were isolated and cultured in vitro,and induced for osteogenic differentiation.Gene expression patterns and functional analysis were assessed through quantitative RT-PCR and RNA-seq.Results:Knockout of XLαs in mice led to notably increased cranial suture width(P<0.05),expanded presence of unmineralized areas within cranial bones(P<0.001),and a significant reduction in osteogenic differentiation(P<0.01).Further,RNA-seq analysis revealed that XLαs deficiency disrupted mitochondrial function.Conclusion:XLαs plays a critical regulatory role in the cranial bone development by modulating mitochondrial function,which provides a novel therapeutic strategy for treating cranial developmental anomalies associated with GNAS mutations.

关 键 词：超大型刺激性G蛋白α亚单位 颅骨发育 矿化 线粒体 

分 类 号：R78[医药卫生—口腔医学]