EFFECT OF CASPASE 3 ON BONE METABOLISM

CASPASE 3 对骨代谢的影响

• 批准号: 19592159
• 负责人: AMANO Hitoshi
• 金额: $ 2.91万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19592159/
• 关键词: カスパーゼ3; 破骨細胞; アポトーシス; 骨吸収; 下顎前突症; カスパーゼ; Caspase3; 骨; リモデリング; ミトコンドリア

Apoptosis is defined as programmed cell death, which is characterized by cell contraction and fragmentation, and nuclear aggregation and fragmentation. Various types of molecular signaling control Apoptosis. Caspase3, a type of cysteine protease, can be activated by stimulus, leading to degradation of a broad range of intracellular substances such as PARP and to induction of apoptosis. Approximately one-half of osteoblasts involved in bone formation undergo apoptosis during the process of transformation into osteocytes when embedded within the bone. In addition, osteoclasts are known to enter apoptosis away from the bone surface after bone resorption. Apoptosis in bone-related cells is considered an essential metabolic system in bone structure ; moreover, Caspase3 may play a significant role in this process. We investigated the role of Caspase3 via utility of mice carrying a Caspase3 gene deficiency. Following completion of visual observation and x-ray photography of mouse skulls (8 we … More eks of age), skullcaps from mice with the gene deficiency exhibited quaquaversal (dome-like) formation characterized by an obtuse angle between the eye-ear plane and the anteroposterior diameter of the occipital skull-base in comparison with the wild type ; consequently, growth suppression of the skull was apparent. Moreover, in mice with the gene deficiency, increased membranous ossification and mandibular prognathism were detected with increasing age. Newborn tibias, following fixation as tissue sections by conventional fixation, were decalcified, embedded in paraffin. Mice with the gene deficiency displayed elevated osteoblast OPG mRNA expression in comparison to the wild type. Increased calcification in osteoblasts carrying the gene deficiency was also demonstrated in vitro. There was no significant difference in osteoclast formation between Caspase 3-/- mice and their littermate. In constrast, caspase3 -/- osteoclast increased bone resorbing activity. This study confirmed abnormal skull formation with increased bone formation and resorption in mice lacking the Caspase3 gene, which controls apoptosis. Caspase3 gene maintains a delicate balance between bone formation and bone resorption ; moreover, it adjusts normal skull development via control of apoptosis in osteoblasts and osteoclasts. Less

凋亡定义为程序性细胞死亡，其特征是细胞收缩和破碎，核聚集和碎片化。各种类型的分子信号控制控制凋亡。 caspase3是一种半胱氨酸蛋白，可以通过刺激激活，从而导致广泛的细胞内物质（例如PARP）和凋亡诱导。当嵌入骨骼中时，大约一半参与骨形成的成骨细胞会在转化为骨细胞的过程中经历凋亡。另外，已知破骨细胞在骨骼分辨率后从骨表面渗入凋亡。骨相关细胞中的凋亡被认为是骨结构中必不可少的代谢系统。此外，CASPASE3在此过程中可能起重要作用。我们通过携带caspase3基因缺乏的小鼠的效用来研究caspase3的作用。在完成视觉观察和X射线摄影的鼠标颅骨（8个我们…更多年龄）之后，具有基因缺乏的小鼠的头骨表现出Quaquaverversal（类似圆顶）的形成，其特征在于眼球平面和枕骨颅底骨架的前后直径与野生类型相比；因此，显而易见的是头骨的生长抑制。此外，在患有基因缺乏的小鼠中，随着年龄的增长检测到膜骨化和下颌预后。新生儿胫骨在通过常规固定的固定为组织切片后被脱钙，嵌入石蜡中。与野生型相比，具有基因缺乏症的小鼠表现出升高的成骨细胞OPG mRNA表达。在体外也证明了携带基因缺乏的成骨细胞计算的增加。胱天蛋白酶3 - / - 小鼠及其同窝鼠之间的破骨细胞形成没有显着差异。约束，caspase3 - / - 破骨细胞增加了骨分辨活性。这项研究证实了异常的颅骨形成，在缺乏控制凋亡的CASPASE3基因的小鼠中，骨形成和分辨率增加。 caspase3基因在骨形成和骨骼分辨率之间保持微妙的平衡。此外，它通过控制成骨细胞和破骨细胞的细胞凋亡来调整正常的头骨发育。较少的