Expression of mouse HtrA1 serine protease in normal bone and cartilage and its upregulation in joint cartilage damaged by experimental arthritis
Expression of mouse HtrA1 serine protease in normal bone and cartilage and its upregulation in joint cartilage damaged by experimental arthritis
复制标题
DOI：
10.1016/j.bone.2005.03.015
复制
发表时间：
2005-09-01
期刊：
影响因子：
4.1
通讯作者：
Oka, C
中科院分区：
文献类型：
--
作者：
Tsuchiya, A;Yano, M;Oka, C
据报道，在人类骨关节炎患者的关节中，软骨中HtrA1蛋白的水平升高。为了了解HtrA1在正常成骨以及关节炎发病机制中的作用，我们研究了HtrA1在骨和软骨发育过程中以及在实验性关节炎影响的关节软骨中的表达模式。在骨化开始前，hTRA1在间充质或软骨凝聚中不表达。当凝集物开始骨化时，HtrA1在靠近骨化中心的肥大分化的软骨细胞中开始表达。在成人关节软骨和骨骺生长板中发现的肥大软骨细胞也表达HtrA1。当注射抗胶原抗体和脂多糖诱导关节炎时，静止的软骨细胞进行终末肥大分化，并开始表达HtrA1。这些数据表明，在正常和病理条件下，肥厚性改变都会诱导软骨细胞HtrA1的表达。据报道，HTRA1可抑制转化生长因子-β信号转导。我们发现HtrA1能消化软骨的主要成分，如聚集素、核心蛋白、纤维调素和可溶性的II型胶原。因此，HTRA1可能通过诱导终末肥大软骨细胞分化和通过其转化生长因子-β抑制活性和蛋白酶活性消化软骨基质来促进软骨退变。在骨中，活跃的立方体成骨细胞几乎不表达HtrA1，但扁平并贴附于骨基质的成骨细胞和嵌入骨中的骨细胞对HtrA1的产生呈强阳性。骨基质显示高水平的HtrA1蛋白沉积，类似于转化生长因子-β，提示转化生长因子-β和HtrA1之间存在密切的功能相互作用。(C)2005 Elsevier Inc.保留所有权利。
Levels of HtrA1 protein in cartilage have been reported to elevate in joints of human osteoarthritis patients. To understand roles of HtrA1 in normal osteogenesis as well as in pathogenesis of arthritis, we examine HtrA1 expression pattern during bone and cartilage development and in articular cartilage affected by experimental arthritis. HtrA1 is not expressed in mesenchymal or cartilage condensations before initiation of ossification. When ossification begins in the condensations, the expression of HtrA1 starts in chondrocytes undergoing hypertrophic differentiation near the ossification center. Hypertrophic chondrocytes found in adult articular cartilage and epiphyseal growth plates also express HtrA1. When arthritis is induced by injection of anti-collagen antibodies and lipopolysaccharide, resting chondrocytes proceed to terminal hypertrophic differentiation and start expressing HtrA1. These data suggest that hypertrophic change induces HtrA1 expression in chondrocytes both in normal and pathological conditions. HtrA1 has been reported to inhibit TGF-beta signaling. We show that HtrA1 digests major components of cartilage, such as aggrecan, decorin, fibromodulin, and soluble type II collagen. HtrA1 may, therefore, promote degeneration of cartilage by inducing terminal hypertrophic chondrocyte differentiation and by digesting cartilage matrix though its TGF-beta inhibitory activity and protease activity, respectively. In bone, active cuboidal osteoblasts barely express HtrA1, but osteoblasts which flatten and adhere to the bone matrix and osteocytes embedded in bone are strongly positive for HtrA1 production. The bone matrix shows a high level of HtrA1 protein deposition akin to that of TGF-beta, suggesting a close functional interaction between TGF-beta and HtrA1. (c) 2005 Elsevier Inc. All rights reserved.