The nitric oxide donor glyceryl trinitrate increases subchondral bone sclerosis and cartilage degeneration following ovine meniscectomy

被引:31
作者
Cake, MA [1 ]
Read, RA
Appleyard, RC
Hwa, SY
Ghosh, P
机构
[1] Murdoch Univ, Sch Vet & Biomed Sci, Perth, WA 6105, Australia
[2] Univ New S Wales, Orthopaed Res Inst, St George Hosp, Kensington, NSW 2033, Australia
[3] Natl Def Med Ctr, Dept Orthopaed, TriServ Gen Hosp, Taipei, Taiwan
[4] Univ Sydney, Inst Bone & Joint Res, Royal N Shore Hosp, Sydney, NSW 2006, Australia
基金
澳大利亚研究理事会;
关键词
glyceryl trinitrate; nitric oxide; osteoarthritis; subchondral bone;
D O I
10.1016/j.joca.2004.08.012
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
Aim: To examine the effect of glyceryl trinitrate (GTN), a nitric oxide (NO) donor compound, on the concurrent progression of cartilage and subchondral bone changes in an ovine meniscectomy model of osteoarthritis (OA). Methods: Bilateral lateral meniscectomy (MX) was performed on 12 ewes to induce OA. Six were treated with topical GTN (0.7 mg/kg twice weekly) (MX + GTN). Six other sheep formed non-operated controls (NOC). After sacrifice at six months, the subchondral bone density (BMD) of the lateral and medial femoral condyles (LFC, MFC) and tibial plateau (LTP, MTP) was assessed by DEXA. Dynamic biomechanical testing was performed across the MTP and LTP. Histological sections from each region were scored qualitatively and the thickness of the subchondral bone plate (SCB) was determined by image analysis. Results: MX + GTN displayed significantly greater SCB thickness relative to MX in the LFC (mean increase +88% and +42%, respectively) and the MFC. SCB BMD was 10-12% greater in MX + GTN relative to MX in the LFC, LTP and MTP. MX + GTN sheep also showed greater increases in some histopathology variables, greater central erosion of the LTP, and changes in dynamic stiffness (decreased) and phase lag (increased) in the outer zone of the LTP. Conclusions: Treatment with GTN significantly increased subchondral bone thickness and density during subchondral remodelling following meniscectomy. In addition, it slightly but significantly worsened degeneration of cartilage structure and function. These results suggest that clinical use of GTN may accelerate both cartilage degeneration and subchondral bone sclerosis if used in the presence of OA, and demonstrate that NO has the potential be an important mediator of the subchondral bone changes seen in OA. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:974 / 981
页数:8
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