EFFECT OF CASPASE 3 ON BONE METABOLISM

细胞凋亡被定义为细胞程序性死亡，其特征是细胞收缩和碎裂，以及核聚集和碎裂。多种类型的分子信号控制着细胞的凋亡。Caspase3是一种半胱氨酸蛋白酶，可以被刺激激活，导致广泛的细胞内物质如PARP的降解，并诱导细胞凋亡。大约一半参与骨形成的成骨细胞在植入骨内后，在转化为骨细胞的过程中会发生凋亡。此外，已知破骨细胞在骨吸收后离开骨表面进入凋亡。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Caspase3可能在这一过程中起着重要的作用。我们通过利用携带Caspase3基因缺陷的小鼠来研究Caspase3的作用。在完成对小鼠头骨的目测和X射线摄影(8WE…与野生型相比，该基因缺陷小鼠的头盖骨呈四方形(圆顶状)，其特征是眼耳平面和枕骨颅底的前后直径之间存在钝角；因此，头骨的生长受到明显的抑制。此外，在基因缺失的小鼠中，随着年龄的增长，膜骨化和下颌前突增加。新生胫骨常规固定后制成组织切片，脱钙，石蜡包埋。与野生型相比，该基因缺失的小鼠显示出成骨细胞OPG mRNA的表达增加。携带该基因缺陷的成骨细胞的钙化增加在体外也被证明。Caspase3-/-小鼠与其仔鼠破骨细胞的形成无显著差异。相比之下，caspase3-/-破骨细胞增加了骨吸收活性。这项研究证实，在缺乏控制细胞凋亡的Caspase3基因的小鼠中，头骨形成异常，骨形成和骨吸收增加。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凋亡来调节正常的颅骨发育。较少

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