EFFECT OF CASPASE 3 ON BONE METABOLISM

CASPASE 3 对骨代谢的影响

基本信息

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

项目摘要

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

细胞凋亡被定义为程序性细胞死亡，其特征是细胞收缩和破碎，细胞核聚集和破碎的多种类型的分子信号控制细胞凋亡，Caspase3是一种半胱氨酸蛋白酶，受到刺激后可被激活，导致降解。参与骨形成的成骨细胞在嵌入骨细胞的过程中，大约有一半会发生细胞凋亡。此外，破骨细胞在骨吸收后进入远离骨表面的细胞凋亡被认为是骨结构中的重要代谢系统；此外，我们研究了Caspase3可能在该过程中发挥重要作用。 Caspase3 通过携带 Caspase3 基因缺陷的小鼠的作用来发挥作用在对小鼠头骨（8 岁）进行目视观察和 X 射线摄影后，来自具有基因缺陷的小鼠的黄盖帽表现出。与野生型相比，其特征是眼耳平面和枕骨颅底前后径之间呈钝角，因此，头骨的生长受到明显抑制。随着年龄的增长，检测到基因缺陷、膜性骨化增加和下颌前突。新生儿胫骨通过常规固定固定为组织切片后，进行脱钙、包埋。与野生型相比，具有基因缺陷的小鼠的成骨细胞 OPG mRNA 表达增加，体外实验也证明了携带该基因缺陷的小鼠的破骨细胞形成没有显着差异。相比之下，caspase3 -/- 破骨细胞增加了缺乏 Caspase3 基因的小鼠的颅骨形成和骨吸收增加。细胞凋亡控制细胞凋亡。Caspase3基因在骨形成和骨吸收之间维持微妙的平衡；此外，它还通过控制成骨细胞和破骨细胞的细胞凋亡来调节正常的颅骨发育。