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29 April 2019 : Animal Research  

Estrogen Modulates Cartilage and Subchondral Bone Remodeling in an Ovariectomized Rat Model of Postmenopausal Osteoarthritis

Xiao Xu1234ABCDF, Xingfu Li123BCDEF, Yujie Liang56ABC, Yangkan Ou23BE, Junfeng Huang23BCD, Jianyi Xiong23CD, Li Duan23ABE, Daping Wang1234ADFG*

DOI: 10.12659/MSM.916254

Med Sci Monit 2019; 25:3146-3153

Abstract

BACKGROUND: Estrogen levels regulate changes in osteoarthritis (OA) by inhibiting degradation of the extracellular matrix. Recent in vitro studies have also shown the role of microRNA-140-5p (miR-140-5p). This study aimed to investigate the role of estrogen deficiency, selective modulation of expression of the estrogen receptor (ER), and expression of miR-140-5p in cartilage and subchondral bone remodeling in an ovariectomized rat model of postmenopausal OA.

MATERIAL AND METHODS: Female Sprague-Dawley rats included two model groups, ovariectomized (OVX) rats and rats with destabilization of the medial meniscus (DMM) rats. Two months after surgery, estrogen levels were measured by the enzyme-linked immunosorbent assay (ELISA). Three-dimensional (3D) micro-computed tomography (micro-CT) was used to image the knee joints. Rats were treated with subcutaneous injection of estrogen (E2) or the selective estrogen receptor modulator (SERM), raloxifene (RAL), for one month. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-140-5p in serum, and histology of the knee joint cartilage and bone was performed.

RESULTS: In the ovariectomized rat model of OA, estrogen therapy reduced the degree of cartilaginous degeneration, while treatment with raloxifene showed no significant effect. Expression levels of miR-140-5p in the OA model group were significantly lower than the control group. Micro-CT showed that in the model group, anterior cruciate ligament dislocation and subchondral bone density were significantly reduced.

CONCLUSIONS: In an ovariectomized rat model of postmenopausal OA, estrogen deficiency resulted in resorption of subchondral bone and degeneration of articular cartilage.

Keywords: Estrogens, MicroRNAs, Osteoarthritis, Raloxifene, Anterior Cruciate Ligament, Bone Density, Bone Remodeling, Bone and Bones, Cartilage, Cartilage, Articular, Disease Models, Animal, Extracellular Matrix, Knee Joint, Ovariectomy, Postmenopause, Rats, Rats, Sprague-Dawley, Receptors, Estrogen

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750