Mechanical factors influence the expression of endostatin - an inhibitor of angiogenesis - in tendons
Mechanical factors influence the expression of endostatin - an inhibitor of angiogenesis - in tendons
复制标题
DOI：
10.1016/s0736-0266(02)00262-0
复制
发表时间：
2003-07-01
影响因子：
2.8
通讯作者：
Mentlein, R
中科院分区：
文献类型：
--
作者：
Pufe, T;Petersen, W;Mentlein, R
肌腱无血管区易发生退行性改变和自发断裂。因此，我们采用免疫组织化学和生化方法分析内源性血管生成抑制因子内皮抑素在人胎儿和成人肌腱中的表达。此外，为了阐明参与血管调节的因素，我们将大鼠肌腱细胞原代培养物置于间歇静水压力（0.2 MPa, 0.1 Hz）下24 h，并通过ELISA测定内皮抑素含量和条件培养基对人脐静脉内皮细胞（HUVEC）增殖的影响。在胎儿肌腱中，ELISA可定量测定高内皮抑素水平，而在成人组织中，内皮抑素水平较低。在胎儿肌腱中，内皮细胞也可以免疫染色内皮抑素，但主要在成纤维细胞中。成人跟腱内皮抑素免疫染色仅限于内皮细胞。在胫骨后肌腱中，作为“缠绕”的一个例子，内皮抑素免疫染色在内踝附近的纤维软骨中保持阳性。内皮抑素抗体密集染色的纤维软骨细胞为i型胶原，阳性纤维软骨。因子VIII免疫染色显示该区域大部分无血管。肌腱细胞单层培养释放可测量量的内皮抑素到其培养上清液中。应用间歇静水压力显著增加内皮抑素表达。间歇静水压力培养的肌腱成纤维细胞条件培养基对HUVEC的增殖具有剂量依赖性。内皮抑素在成人滑动肌腱中的空间表达表明，机械因素参与了这种抗血管生成因子的调节。因此，暴露于间歇静水压力下的肌腱细胞通过体液因子抑制内皮细胞增殖，产生内皮抑素。这些发现支持了这样一种观点，即肌腱无血管区的发展和维持可能是由机械诱导的抗血管生成因子上调引起的。(C) 2003骨科研究学会。Elsevier Science Ltd.出版。版权所有。
Avascular zones of tendons are predisposed for degenerative changes and spontaneous rupture. Therefore, we analyzed the expression of the endogenous angiogenesis inhibiting factor endostatin in human fetal and adult tendons by immunohistochemical and biochemical methods., Moreover, to elucidate factors involved in the regulation of vascularity, we exposed primary cultures of rat tendon cells to intermittent hydrostatic pressure (0.2 MPa, 0.1 Hz for 24 h), and measured the endostatin content by ELISA and the effect of the conditioned medium to the proliferation of human umbilical vein endothelial cells (HUVEC).In fetal tendons high endostatin levels could be quantified by ELISA whereas low levels were found in adult tissue. In fetal tendons endostatin could also be immunostained in endothelial cells but mainly in fibroblasts. In adult Achilles tendons endostatin immunostaining was restricted to endothelial cells. In the tibialis posterior tendon-as an example for "wrap around"-endostatin immunostaining remained positive in the fibrocartilage adjacent to the medial malleolus. Fibrochondrocytes of the type It collagen, positive fibrocartilage were intensively stained with the endostatin antibody. Factor VIII immunostaining showed that this region was largely avascular. Monolayer cultures of tendon cells released measurable amounts of endostatin into their culture supernatants. Application of intermittent hydrostatic pressure increased endostatin expression significantly. The conditioned media of tendon fibroblasts cultivated under intermittent hydrostatic pressure inhibited the proliferation of HUVEC in a dose dependent way.The spatial expression of endostatin in adult gliding tendons suggests that mechanical factors are involved in the regulation of this anti-angiogenic factor. In accordance, tendon cells exposed to intermittent hydrostatic pressure inhibit endothelial cell proliferation via humoral factors and produce endostatin. These findings support the view that the development and maintenance of avascular zones in tendons might be caused by a mechanically induced upregulation of anti-angiogenic factors. (C) 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.