Ovariectomized rats as a model of postmenopausal osteoarthritis: validation and application

Arthritis Research & Therapy

Pernille Høegh-Andersen²  László B Tankó¹  Thomas L Andersen²  Carina V Lundberg²  John A Mo²  Anne-Marie Heegaard²  Jean-Marie Delaissé²  Stephan Christgau² 

[1] Center for Clinical and Basic Research, Ballerup Byvej 222, 2750 Ballerup, Denmark

[2] Nordic Bioscience A/S, Herlev Hovedgade 207, 2730 Herlev, Denmark

关键词: selective estrogen receptor modulator;    ovariectomy;    osteoarthritis;    estrogen;   

Others  :  1101283
DOI  :  10.1186/ar1152

 received in 2003-10-17, accepted in 2004-01-21,  发布年份 2004

【 摘 要 】

We aimed to assess the effect of ovariectomy on cartilage turnover and degradation, to evaluate whether ovariectomized (OVX) rats could form an experimental model of postmenopausal osteoarthritis. The effect of ovariectomy on cartilage was studied using two cohorts of female Sprague–Dawley rats, aged 5 and 7 months. In a third cohort, the effect of exogenous estrogen and a selective estrogen receptor modulator was analyzed. Knee joints were assessed by histological analysis of the articular cartilage after 9 weeks. Cartilage turnover was measured in urine by an immunoassay specific for collagen type II degradation products (CTX-II), and bone resorption was quantified in serum using an assay for bone collagen type I fragments (CTX-I). Surface erosion in the cartilage of the knee was more severe in OVX rats than in sham-operated animals, particularly in the 7-month-old cohort (P = 0.008). Ovariectomy also significant increased CTX-I and CTX-II. Both the absolute levels of CTX-II and the relative changes from baseline seen at week 4 correlated strongly with the severity of cartilage surface erosion at termination (r = 0.74, P < 0.01). Both estrogen and the selective estrogen receptor modulator inhibited the ovariectomy-induced acceleration of cartilage and bone turnover and significantly suppressed cartilage degradation and erosion seen in vehicle-treated OVX rats. The study indicates that estrogen deficiency accelerates cartilage turnover and increases cartilage surface erosion. OVX rats provide a useful experimental model for the evaluation of the chondroprotective effects of estrogens and estrogen-like substances and the model may be an in vivo representation of osteoarthritis in postmenopausal women.

【 授权许可】

   
2004 Høegh-Andersen et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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