骨关节炎软骨下骨中视网膜母细胞瘤RB1-诱导卷曲蛋白1的表达及作用 |
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作者姓名: | 李俊彦 方航 冯晓峰 蔡道章 |
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作者单位: | 南方医科大学第三附属医院,广东省广州市 510630 |
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基金项目: | 国家自然科学基金项目(81371990),项目负责人:蔡道章;国家自然科学基金项目(81601945),项目负责人:方航~~ |
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摘 要: |
文题释义:视网膜母细胞瘤RB1-诱导卷曲蛋白1(RB1-inducible coiled-coil 1,RB1CC1):是一种相对分子质量为200的FAK家族相互作用蛋白,最初通过酵母双杂交筛选鉴定为Pyk2相互作用蛋白,并可作为RB1基因的潜在调节因子,参与肿瘤细胞的周期调控。RB1CC1多在心脏、睾丸、肌肉骨骼以及小鼠胚胎等组织中大量表达,对细胞的生长、分化、凋亡和自噬起到重要的调控作用。
骨涎蛋白:是一种由成骨细胞、破骨细胞合成的磷酸化糖蛋白,相对分子质量为75,含有约300个氨基酸。在骨组织中大量表达,可特异性定位于矿化的骨组织内,参与成骨细胞和破骨细胞的骨代谢活动,是成骨细胞矿化成熟的标志。骨涎蛋白的RGD序列基因可与血管内皮细胞的整合素结合,从而引导软骨组织内血管形成。
背景:骨关节炎以关节软骨的退变和软骨下骨的重建为主要病理特征。骨关节炎的具体发病机制目前仍未清楚,大部分研究以软骨与软骨下骨为主要切入点,探索疾病过程中的分子机制和信号通路变化,为骨关节炎的诊断与治疗提供新的生物靶点和研究方向。
目的:探讨在骨关节炎进程中软骨下骨RB1CC1的表达情况。
方法:8周龄C57小鼠随机分为实验组和假手术组,实验组又随机分为4周和8周2个亚组。实验组小鼠行右侧膝关节内侧半月板胫骨韧带切除,游离内侧半月板,诱导骨关节炎;假手术组小鼠则仅切开关节囊而不行内侧韧带切除和半月板游离。实验方案于2017-12-13经南方医科大学第三附属医院动物实验伦理委员会批准,批准号为No.44007200038731。
结果与结论:与假手术组相比,实验组骨关节炎RSI评分均显著升高,关节软骨面Ⅱ型胶原表达降低,软骨下骨中的RB1CC1表达逐渐升高,RB1CC1与成骨相关指标BSP2的表达趋势有一致性;提示随着骨关节炎进程的发展,软骨下骨的RB1CC1表达逐渐增多,可能与促进软骨下骨增生及重塑有关。
ORCID: 0000-0002-2838-3707(蔡道章)
中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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关 键 词: | 骨关节炎 软骨下骨 RB1CC1 成骨 骨代谢 BSP2 硬化 血管形成 |
收稿时间: | 2019-09-18 |
Expression and role of retinoblastoma RB1-inducible coiled-coil 1 in the subchondral bone of osteoarthritis |
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Authors: | Li Junyan Fang Hang Feng Xiaofeng Cai Daozhang |
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Institution: | The
Third Affiliated Hospital of Southern Medical University, Guangzhou 510630,
Guangdong Province, China |
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Abstract: | BACKGROUND:Osteoarthritis is mainly characterized by degeneration of the articular cartilage and reconstruction of the subchondral bone.The specific pathogenesis of osteoarthritis is still unclear.Most studies have used cartilage and subchondral bone as the main entry point to explore the molecular mechanism and signal pathway changes in the disease progression,providing new biological targets and research direction for the diagnosis and treatment of osteoarthritis.OBJECTIVE:To investigate the expression of RB1-inducible coiled-coil 1(RB1CC1)in the subchondral bone during the development of osteoarthritis.METHODS:Eight-week-old C57 mice were randomly divided into experimental group and sham operation group.Experimental group was then randomly divided into two subgroups of 4 weeks and 8 weeks.In the experimental group,the tibia ligament of the right knee was cut off to dissociate the medial meniscus to induce osteoarthritis.In the sham operation group,only the joint capsule was cut without medial ligament resection and meniscus dissociation.The study was implemented with an experimental animal ethic approval from the Third Affiliated Hospital of Southern Medical University,China(approval No.44007200038731)on December 13,2017.RESULTS AND CONCLUSION:Compared with the sham operation group,the Osteoarthritis Research Society International scores were increased significantly in the experimental group.Compared with the sham operation group,the expression of collagen II was decreased,and RB1CC1 in the subchondral bone was gradually increased in the experimental group,which was consistent with the expression trend of BSP2.To conclude,with the development of osteoarthritis,the expression of RB1CC1 in the subchondral bone is gradually increased,which may be related to the increase of hyperplasia in the subchondral bone and remodeling. |
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Keywords: | osteoarthritis subchondral bone RB1CC1 osteogenesis bone metabolism BSP2 sclerosis angiogenesis |
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