Research of the physiological functions of membrane-type matrix metalloproteinases

在我们的小鼠品系MT 1-MMP基因表达缺陷，骨形态发生严重受损，与过去的报告一致。接下来的问题是要知道在生理状态下骨组织中哪些细胞系负责在骨形态发生过程中表达MT 1-MMP。为了观察MT 1-MMP在骨组织中的有限恢复是否有助于逆转表型，正在构建基于敲除小鼠的条件转基因品系，其中MT 1-MMP的表达在成骨细胞中有限恢复。另一方面，MT 1-MMP在第二次骨化过程中，在骨化中心周围的血管生成中起重要作用。为了更深入地了解这一作用，进行了肌块在I型胶原中的三维培养。在培养期间观察到通过胶原的血管生成。MT 1-MMP缺陷株的肌肉块严重损害血管生成 ...更多信息 与野生型和杂合子相比，MT 1-MMP在新生血管中主要表达于内皮细胞。MT 1-MMP是如何在血管生成中发挥作用的，为什么其他蛋白酶不能充分补偿这些功能，或者MT 1-MMP缺陷小鼠的二次骨化障碍是否主要是由骨周围不良的血管生成引起的。MT5-MMP在小鼠大脑、小脑、海马等神经细胞中均有表达。然而，在MT5-MMP基因缺陷的菌株中未检测到明显的异常。基于MT5-MMP表达的特异性，用来自背路神经节的小鼠神经细胞进行神经突延伸测定，证明神经突的突出在层粘连蛋白上被促进，并且在肝素结合蛋白聚糖上被抑制。加入纯化的可溶性MT5-MMP，后者的抑制作用随着底物的降解而释放，免疫组化检测到内源性MT5-MMP主要在生长锥中表达。MT4-MMP已被证明在大脑额叶皮质、下海马、小脑、肾单位、血管平滑肌细胞、心脏和脾脏红髓中表达。MT4-MMP基因缺失株的组织学观察未见光泽异常。接下来应该进行几项功能分析以了解MT4-MMP在小鼠组织中如何发挥作用。少

In our murine strain deficient in MT1-MMP gene expression, the bone morphogenesis was severely impaired, consistent with the past reports. Next question would be an address to know which cell lineages in bone tissue are responsible to work with expressing MT1-MMP during the bone morphogenesis under the physiologic state. To see if a recovering of the MT1-MMP limitedly in bone tissue helps to revart the phenotype, a conditional transgenic strain is under construction based on the knock-out mice, in which expression of MT1-MMP is recovered restrictedly in osteoblasts. On the other hand, MT1-MMP plays a important role in angiogenesis around the ossification center during the second ossification. In order to understand the role more profoundly, three-dimensional culture of muscle chunks in type-I collagen has been conducted. Angiogenesis through the collagen was observed during the culturing period. The angiogenesis was severely impaired with the mucle chunk of the MT1-MMP deficient strain … More compared to the wild type or the hetero-zygote.MT1-MMP in the new vessels was predominantly expressed in endothelial cells. Questions remains how MT1-MMP plays a role in angiogenesis, why other proteinases can not compensate the functions sufficiently, or whether the impairment in second ossification in MT1-MMP deficient mice is induced predominantly by the poor angiogenesis around the bone. The conditional transgenic mice could provide us with some hints to ask for the queries.MT5-MMP has been found to expressed at neural cells such in cerebrum, cerebellum, and hypocampus. However, no distinct abnormality has been detected in a strain deficient in MT5-MMP gene. Based on the specificity in MT5-MMP expression, a neurite extension assay was performed with the murine neural cells derived from dorsal route ganglia, demonstrated that the protrusion of the neurite was facilitated on laminin, and inhibited on heparin binding proteoglycan. Adding a soluble MT5-MMP purified, The latter inhibition has released with a degradation of the substrate.Immunohistochemically, endogenous MT5-MMP was detected predominantly at the growth cone.MT4-MMP has been shown to be expressed such at a cortex in the frontal lobe of brain, hypocampus, cerebellum, nephron, smooth muscle cells in the vessels, heart, and red pulp in spleen. Histologically, no gloss abnormality was found in a strain- deficient in MT4-MMP gene. Several functional analyzes should be performed next to know how MT4-MMP plays roles in murine tissue. Less