Ovariectomy alters the structural and biomechanical properties of ovine femoro-tibial articular cartilage and increases cartilage NOS

被引:33
作者
Cake, MA [1 ]
Appleyard, RC
Read, RA
Smith, MM
Murrell, GAC
Ghosh, P
机构
[1] Murdoch Univ, Sch Vet & Biomed Sci, Perth, WA 6105, Australia
[2] Univ New S Wales, St George Hosp, Orthopaed Res Inst, Kensington, NSW 2033, Australia
[3] Univ Sydney, Royal N Shore Hosp, Inst Bone & Joint Res, Sydney, NSW 2006, Australia
基金
澳大利亚研究理事会;
关键词
ovariectomy; sheep; cartilage biomechanics; nitric oxide radical;
D O I
10.1016/j.joca.2005.07.001
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
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.
引用
收藏
页码:1066 / 1075
页数:10
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