Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues
Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues
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DOI：
10.1002/jcb.21224
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发表时间：
2007-06-01
影响因子：
4
通讯作者：
Markwald, Roger R.
中科院分区：
文献类型：
--
作者：
Norris, Russell A.;Damon, Brook;Markwald, Roger R.
骨膜蛋白主要表达于承受恒定机械应力的富含胶原的纤维结缔组织中，包括：心脏瓣膜、肌腱、软骨膜、角膜和牙周韧带。基于这些数据，我们假设骨膜蛋白可以调节胶原纤维的形成，从而影响结缔组织的生物力学特性。免疫沉淀和免疫金透射电镜实验表明，骨膜蛋白能够直接与I型胶原相互作用。为了分析骨膜蛋白在I型胶原纤维形成中的潜在作用，我们制作了基因靶向小鼠。透射电子显微镜和形态计量学分析显示，骨膜蛋白敲除小鼠皮肤真皮的胶原纤维直径减少，表明异常的I型胶原纤维形成。此外，差示扫描量热法（DSC）显示，骨膜蛋白敲除小鼠的胶原变性温度较低，反映了胶原交联水平降低。骨膜素皮肤标本和房室瓣膜移植实验的功能生物力学特性直接证明了骨膜素对结缔组织粘弹性特性的调节作用。总的来说，这些数据首次证明了骨膜蛋白可以调节I型胶原纤维的形成，从而作为纤维结缔组织生物力学特性的重要介质。
Periostin is predominantly expressed in collagen-rich fibrous connective tissues that are subjected to constant mechanical stresses including: heart valves, tendons, perichondrium, cornea, and the periodontal ligament (PDL). Based on these data we hypothesize that periostin can regulate collagen I fibrillogenesis and thereby affect the biomechanical properties of connective tissues. Immunoprecipitation and immunogold transmission electron microscopy experiments demonstrate that periostin is capable of directly interacting with collagen I. To analyze the potential role of periostin in collagen I fibrillogenesis, gene targeted mice were generated. Transmission electron microscopy and morphometric analyses demonstrated reduced collagen fibril diameters in skin dermis of periostin knockout mice, an indication of aberrant collagen I fibrillogenesis. In addition, differential scanning calorimetry (DSC) demonstrated a lower collagen denaturing temperature in periostin knockout mice, reflecting a reduced level of collagen cross-linking. Functional biomechanical properties of periostin null skin specimens and atrioventricular (AV) valve explant experiments provided direct evidence of the role that periostin plays in regulating the viscoelastic properties of connective tissues. Collectively, these data demonstrate for the first time that periostin can regulate collagen I fibrillogenesis and thereby serves as an important mediator of the biomechanical properties of fibrous connective tissues.