PARTICIPATION OF CATHEPSIN L ON ORTHODONTIC TOOTH

组织蛋白酶L对正畸牙齿的影响

基本信息

批准号：
06672056
负责人：
SUMITANI Koji
金额：
$ 1.41万
依托单位：
THE UNIVERSITY OF TOKUSHIMA
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672056/
关键词：
Cathepsin L Osteoclast(s)Bone resorption Calcitonin Proton カテプシン歯牙移動

项目摘要

Osteoclasts are multinucleated giant cells responsible for the resorption of the calcified extracellular bone matrix. The degradation of the bone matrix protein including type I collagen is a key process for osteoclastic bone resorption. It has been suggested that lysosomal cysteine proteinase in osteoclasts is essential to degrade bone collagen, but the proteinase(s) for this collagenolysis have not been identified.In this study, the participation of cathepsin L on osteoclastic bone resorption was investigated and the results obtained were as follows.1) In cultured rat bone marrow cells, parathyroid hormone (PTH)-stimulated bone resorption was markedly suppressed by all of specific and non-specific inhibitors of cathepsin L tested but not by a specific inhibitor (CA-074) of cathepsin B.2) In rats with bone resorption stimulated by a low calcium diet, serum calcium level was decreased by an intraperitoneal injection of cathepsin Linhibitors but not by CA-074.3) Activities of cathepsin L and B were shown to be more than 80% of total proteinase activity in the culture medium of rat bone marrow cells.4) In bone marrow cells cultured on bone slices, PTH increased both bone resorption and cathepsin L activity in the medium and these increases were suppressed by calcitonin.5) The cultured bone marrow cells secreted cathepsin L as 39kD molecule and the secretion was suppressed by calcitonin.6) The 39kD cathepsin L purified from rat long bones was converted to 25kD cathepsin L under acidic condition.7) Rat long bone-derived 25kD cathepsin L as well as purified cathepsin L of rat liver degraded type I collagen at pH 4.05.0.These results suggested that cathepsin L secreted from osteoclast plays a crucial role in the degradation of bone matrix proteins including type I collagen during bone resorption.

破骨细胞是负责吸收钙化的细胞外骨基质的多核巨细胞。包括I型胶原在内的骨基质蛋白的降解是破骨细胞骨吸收的关键过程。有人提出，破骨细胞中的溶酶体半胱氨酸蛋白酶对于降解骨胶原至关重要，但这种胶原溶解的蛋白酶尚未确定。在本研究中，研究了组织蛋白酶L对破骨细胞骨吸收的参与，并获得了结果如下。1）在培养的大鼠骨髓细胞中，所有特异性和非特异性组织蛋白酶抑制剂均显着抑制甲状旁腺激素（PTH）刺激的骨吸收L 已测试，但未通过组织蛋白酶特定抑制剂 (CA-074) B.2) 在低钙饮食刺激骨吸收的大鼠中，腹膜内注射组织蛋白酶 Linhibitors 会降低血清钙水平，但 CA-074.3 不会降低血清钙水平在大鼠骨髓细胞的培养基中，组织蛋白酶 L 和 B 的活性超过总蛋白酶活性的 80%。4) 在骨培养的骨髓细胞中切片中，PTH 增加了培养基中的骨吸收和组织蛋白酶 L 活性，并且这些增加被降钙素抑制。5) 培养的骨髓细胞分泌组织蛋白酶 L 作为 39kD 分子，这种分泌被降钙素抑制。6) 纯化的 39kD 组织蛋白酶 L大鼠长骨来源的25kD组织蛋白酶L在酸性条件下转化为25kD组织蛋白酶L。7)大鼠长骨来源的25kD组织蛋白酶L以及纯化的大鼠肝脏组织蛋白酶L在pH 4.05.0下降解I型胶原。这些结果表明破骨细胞分泌的组织蛋白酶L在骨吸收过程中对包括I型胶原在内的骨基质蛋白的降解起着至关重要的作用。