Raloxifene retards cartilage degradation and improves subchondral bone micro-architecture in ovariectomized rats with patella baja-induced - patellofemoral joint osteoarthritis
Raloxifene retards cartilage degradation and improves subchondral bone micro-architecture in ovariectomized rats with patella baja-induced - patellofemoral joint osteoarthritis
复制标题
雷洛昔芬可延缓患有髌骨诱发的髌股关节骨关节炎的卵巢切除大鼠的软骨退化并改善软骨下骨微结构
DOI：
10.1016/j.joca.2019.06.014
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发表时间：
2020-03-01
影响因子：
7
通讯作者：
Zhang, L.
中科院分区：
文献类型：
--
作者：
Bei, M. -J.;Tian, F. -M.;Zhang, L.
目的：雌激素缺乏引起的软骨下骨（SB）的异常重建与骨关节炎（OA）的发生有关。雷洛昔芬（RAL）通常用于治疗绝经后骨质疏松症（OP）。然而，很少有人知道它对OA合并雌激素缺乏的影响。本研究旨在评估RAL对髌骨baja诱导的髌股关节OA（PFJOA）的疗效在卵巢切除大鼠model.Design：髌韧带缩短（PLS）和卵巢切除术（OVX）同时进行在3个月大的雌性Sprague-Dawley大鼠，这是与RAL（10毫克/公斤/天）或车辆在术后72小时10周。采用免疫组化（IHC）、实时荧光定量PCR（PCR）、抗酒石酸酸性磷酸酶（TRAP）染色、酶联免疫吸附试验（ELISA）、显微CT（mu CT）、组织形态学和行为学分析等方法对PFJOA进行评价。组织形态学分析显示，PFJOA明显加重OVX和明显减轻RAL。此外，RAL通过在蛋白和mRNA水平上降低MMP-13、ADAMTS-4和caspase-3以及增加Col-II和聚集蛋白聚糖来改善软骨代谢。此外，RAL显着改善骨量和SB微结构，并减少破骨细胞数量和血清骨钙素和CTX-I水平。虽然RAL显示出基于机械性异常性疼痛测试的疼痛敏感性降低的趋势，但该结果在统计学上并不显著。这些发现表明RAL治疗延缓了卵巢切除大鼠模型中的PFJOA进展，提示它可能是改善伴有绝经后OP的PFJOA进展的潜在候选药物。（C）2019由Elsevier Ltd代表国际骨关节炎研究协会发布。
Objective: Abnormal remodeling of subchondral bone (SB) induced by estrogen deficiency has been shown to be involved in osteoarthritis (OA). Raloxifene (RAL) is commonly used to treat postmenopausal osteoporosis (OP). However, little is known about its effects on OA combined with estrogen deficiency. This study was performed to evaluate the efficacy of RAL on patella baja-induced patellofemoral joint OA (PFJOA) in an ovariectomized rat model.Design: Patellar ligament shortening (PLS) and ovariectomy (OVX) were performed simultaneously in 3-month-old female Sprague-Dawley rats, which were treated with RAL (10 mg/kg/day) or vehicle at 72 h postoperatively for 10 weeks. PFJOA was assessed by immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosor- bent assay (ELISA), micro-computed tomography (mu CT), histomorphology and behavioral analyses.Results: X-ray examinations showed that patella baja was successfully established by PLS. Histomorphological analysis revealed that PFJOA was significantly exacerbated by OVX and markedly alleviated by RAL. Moreover, RAL improved cartilage metabolism by decreasing MMP-13, ADAMTS-4, and caspase-3 and increasing Col-II and aggrecan at both the protein and mRNA levels. Furthermore, RAL markedly improved bone mass and SB microarchitecture and reduced osteoclast numbers and the serum osteocalcin and CTX-I levels. Although RAL showed a trend toward reducing pain sensitivity based on mechanical allodynia testing, this result was not statistically significant.Conclusion: These findings demonstrate that RAL treatment retards PFJOA progression in an ovariectomized rat model, suggesting that it may be a potential candidate for amelioration of the progression of PFJOA accompanied by postmenopausal OP. (C) 2019 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.