Ovariectomy alters the structural and biomechanical properties of ovine femoro-tibial articular cartilage and increases cartilage NOS
Ovariectomy alters the structural and biomechanical properties of ovine femoro-tibial articular cartilage and increases cartilage NOS
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DOI：
10.1016/j.joca.2005.07.001
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发表时间：
2005-12-01
影响因子：
7
通讯作者：
Ghosh, P
中科院分区：
文献类型：
--
作者：
Cake, MA;Appleyard, RC;Ghosh, P
目的：研究卵巢切除后雌激素耗竭对绵羊股骨-胫骨关节软骨(AC)结构和生物力学性能的影响，以及这些组织产生诱导型一氧化氮合酶(INOS)和硝基酪氨酸的情况。方法：6只老年绵羊接受手术去卵巢(OVX)，6只作为对照。术后26周进行胫骨平台AC动态生物力学压痕测试。取胫骨内侧平台和胫骨外侧平台(LTP)、股骨内侧和外侧髁部(MFC、LFC)和髌骨AC进行组织学切片，观察组织病理学、甲苯胺蓝染色强度和胶原双折射强度。结果：去势绵羊LTP-AC的相位滞后明显减少(10.9+/-2.2°vs12.1+/-2.3°，P<；0.0001)。去势绵羊LTP软骨厚度减少(P=0.0002)，并伴有动态剪切模数的局部变化。甲苯胺蓝在髌骨、LFC和MFC的染色强度降低。组织学检查显示OVX动物MFC的组织病理学评分较高，LTP中的胶原双折射强度图发生改变。诱导型一氧化氮合酶在AC中表达增强(P=0.008)，而硝基酪氨酸在AC(P<；0.0001)中表达增强。结论：OVX诱导的雌激素耗竭导致股骨-胫骨软骨局部变薄，生物力学和组织学改变提示蛋白多糖和胶原大分子组装的内容和/或结构组织紊乱。观察到的软骨诱导型一氧化氮合酶的上调提示了这些基质改变的可能机制。(C)2005年国际骨性关节炎研究会。爱思唯尔有限公司出版。保留所有权利。
Objective: To examine the effect of oestrogen depletion produced by surgical ovariectomy on the structural and biomechanical properties of ovine femoro-tibial articular cartilage (AC), and the production of inducible nitric oxide synthase (iNOS) and nitrotyrosine by these tissues.Methods: Six aged ewes were surgically ovariectomised (OVX), while six were used as unoperated controls. Dynamic biomechanical indentation testing of tibial plateau AC was performed at 26 weeks post-op. Histological sections of medial tibial plateau and lateral tibial plateau (LTP), medial and lateral femoral condyles (MFC, LFC) and patellar AC were examined for histopathology, toluidine blue staining intensity, and patterns of collagen birefringence intensity. Immunoreactivity for iNOS and nitrotyrosine was assessed in full-thickness biopsy plugs of LFC and patellar AC, and patellar AC explants were cultured to determine in vitro NO release.Results: Phase lag was reduced overall in LTP-AC of OVX sheep (10.9 +/- 2.2 degrees vs 12.1 +/- 2.3 degrees; P < 0.0001). Cartilage thickness was reduced in the LTP of OVX sheep (P = 0.0002), in association with localised changes in dynamic shear modulus. Toluidine blue staining intensity was reduced in the patella, LFC, and MFC. Histological examination revealed greater histopathology scores in the MFC of OVX animals, and altered collagen birefringence intensity plots in the LTP. Immunostaining for iNOS was increased in patella AC (P = 0.008), whilst nitrotyrosine immunoreactivity was increased in patella (P = 0.03) and LFC (P < 0.0001) AC. NO release by patellar AC explants was also elevated.Conclusions: Oestrogen depletion induced by OVX caused regional thinning of femoro-tibial cartilage, with biomechanical and histological changes suggestive of a disturbance in the content and/or structural organisation of the proteoglycan and collagen macromolecular assembly. The observed up-regulation of cartilage iNOS suggests a possible mechanism for these matrix changes. (c) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.