Osteopenia and decreased bone formation in osteonectin-deficient mice
Osteopenia and decreased bone formation in osteonectin-deficient mice
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DOI：
10.1172/jci7039
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发表时间：
2000-04-01
影响因子：
15.9
通讯作者：
Canalis, E
中科院分区：
文献类型：
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作者：
Delany, AM;Amling, M;Canalis, E
骨骼在机械和生理压力下不断重塑，使脊椎动物在成年后能够更新骨骼。骨重塑包括胶原和非胶原细胞外基质蛋白的循环合成和吸收，这一过程中的不平衡可导致骨质疏松症等疾病状态，或更罕见的骨质疏松症。有证据表明，细胞外基质糖蛋白骨连接素或分泌的酸性和富含半胱氨酸的蛋白（BM-40）可能在骨重塑中起重要作用。骨连接素在骨骼中含量丰富，并在骨骼外的活性重塑区域表达。体外研究表明，骨连接素可以结合胶原蛋白，调节血管生成、金属蛋白酶表达、细胞增殖和细胞-基质相互作用。在一些骨质减少的状态下，如成骨不完全和骨脆弱的动物模型，骨连接素的表达减少。为了确定骨连接素在骨中的功能，我们使用接触x线，组织形态学和Northern blot分析来表征骨连接素缺失小鼠的骨骼表型。我们发现，骨连接素缺失小鼠骨形成减少，成骨细胞和破骨细胞的表面和数量减少，导致骨重塑减少，骨平衡为负，造成严重的骨质减少。这些数据表明骨连接素支持脊椎动物骨重塑和骨量的维持。
Bone continuously remodels in response to mechanical and physiological stresses, allowing vertebrates to renew bone as adults. Bone remodeling consists of the cycled synthesis and resorption of collagenous and noncollagenous extracellular matrix proteins, and an imbalance in this process can lead to disease states such as osteoporosis, or more rarely osteopetrosis. There is evidence that the extracellular matrix glycoprotein osteonectin or secreted protein acidic and rich in cysteine (BM-40) may be important in bone remodeling. Osteonectin is abundant in bone and is expressed in areas of active remodeling outside the skeleton. In vitro studies indicate that osteonectin can bind collagen and regulate angiogenesis, metalloproteinase expression, cell proliferation, and cell-matrix interactions. In some osteopenic states, such as osteogenesis imperfecta and selected animal models for bone fragility, osteonectin expression is decreased. To determine the function of osteonectin in bone, we used contact x-ray, histomorphometry and Northern blot analysis to characterize the skeletal phenotype of osteonectin-null mice. We found that osteonectin-null mice have decreased bone formation and decreased osteoblast and osteoclast surface and number, leading to decreased bone remodeling with a negative bone balance and causing profound osteopenia. These data indicate that osteonectin supports hone remodeling and the maintenance of bone mass in vertebrates.