EFFECT OF CASPASE 3 ON BONE METABOLISM

细胞凋亡是以细胞收缩和碎裂、核聚集和碎裂为特征的程序性细胞死亡。各种类型的分子信号控制细胞凋亡。半胱氨酸蛋白酶3（Caspase 3）是一种半胱氨酸蛋白酶，可被刺激激活，导致广泛的细胞内物质如PARP的降解和诱导细胞凋亡。大约一半参与骨形成的成骨细胞在包埋在骨内时在转化成骨细胞的过程中经历凋亡。此外，已知破骨细胞在骨吸收后远离骨表面进入凋亡。骨相关细胞的凋亡被认为是骨结构中一个重要的代谢系统，而Caspase 3可能在这一过程中发挥重要作用。我们通过使用携带Caspase 3基因缺陷的小鼠来研究Caspase 3的作用。在完成小鼠颅骨的视觉观察和X射线摄影后（8 we ...更多信息 Eks的年龄），与野生型相比，来自基因缺陷小鼠的头盖骨表现出quaquaescent（圆顶样）形成，其特征在于眼耳平面和枕骨颅底前后直径之间的钝角;因此，头骨的生长抑制是明显的。此外，在基因缺陷的小鼠中，随着年龄的增长，检测到膜骨化和下颌骨骨化增加。新生儿胫骨，通过常规固定作为组织切片固定后，脱钙，石蜡包埋。与野生型相比，基因缺陷的小鼠显示成骨细胞OPG mRNA表达升高。在体外实验中也证明了携带基因缺陷的成骨细胞钙化增加。Caspase 3-/-小鼠与其同窝小鼠之间的破骨细胞形成无显著差异。在Cystast中，半胱天冬酶3-/-破骨细胞增加骨吸收活性。这项研究证实了在缺乏控制细胞凋亡的Caspase 3基因的小鼠中，颅骨形成异常，骨形成和骨吸收增加。Caspase 3基因在骨形成和骨吸收之间维持着一种微妙的平衡，并通过控制成骨细胞和破骨细胞的凋亡来调节正常的颅骨发育。少

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