Wu Qingyun, Xiong Xueting, Zhang Xinle, Lu Jiaqi, Zhang Xuemei, Chen Wenshuang, Wu Tie, Cui Liao, Liu Yuyu, Xu Bilian
Department of Pharmacology, Guangdong Medical University, No. 2, Wenming Donglu, Xiashan District, Zhanjiang, 524023, Guangdong, People's Republic of China.
Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, 524023, Guangdong, People's Republic of China.
J Bone Miner Metab. 2016 Sep;34(5):500-16. doi: 10.1007/s00774-015-0700-4. Epub 2015 Jul 26.
Numerous studies have demonstrated that rheumatoid arthritis (RA) is often associated with bone loss; however, few experiments have focused on cancellous and cortical bone changes in rats during the process of arthritis. We have investigated bone changes in rats with collagen-induced arthritis (CIA) and have explored the characteristics of how RA induces osteoporosis by means of bone histomorphometry, bone biomechanics studies, bone mineral density studies, micro computer tomography, enzyme-linked immunosorbant assay, immunohistochemistry, and Western blot analysis. Bone mineral density of the femur and lumbar vertebrae and biomechanical properties of the femur were decreased in CIA rats. Trabecular bone volume of the tibia and lumbar vertebrae was decreased whereas bone resorption was increased in CIA rats. Bone formation of the tibial shaft in periosteal surfaces was decreased in CIA rats. Furthermore, the trabecular bone loss in CIA rats was severer at 16 weeks than at 8 weeks, as was cortical bone loss. The serum level of tumor necrosis factor α in CIA rats was increased, and the expression of dickkopf 1 and that of receptor activator of nuclear factor κB (RANKL) ligand (RANKL) in the ankle joints were also increased, but the expression of osteoprotegerin (OPG) was decreased. We conclude that CIA rats developed systemic osteoporosis, and that osteoporosis became more serious with CIA development. The mechanism may be related to the increase of bone resorption in cancellous bone cause by upregulation of the expression of DKK-1 and regulation of the RANKL/RANK/OPG signaling pathway, and the decrease of bone formation in cortical bone caused by an increase in the expression of DKK-1.
大量研究表明类风湿关节炎（RA）常与骨质流失相关；然而，很少有实验关注关节炎过程中大鼠松质骨和皮质骨的变化。我们研究了胶原诱导性关节炎（CIA）大鼠的骨变化，并通过骨组织形态计量学、骨生物力学研究、骨密度研究、微型计算机断层扫描、酶联免疫吸附测定、免疫组织化学和蛋白质印迹分析，探讨了RA诱导骨质疏松的特征。CIA大鼠的股骨和腰椎骨密度以及股骨的生物力学性能降低。CIA大鼠胫骨和腰椎的骨小梁体积减少，而骨吸收增加。CIA大鼠胫骨骨干骨膜表面的骨形成减少。此外，CIA大鼠在16周时的骨小梁骨丢失比8周时更严重，皮质骨丢失情况也是如此。CIA大鼠血清肿瘤坏死因子α水平升高，踝关节中Dickkopf 1（DKK-1）和核因子κB受体激活剂配体（RANKL）的表达也增加，但骨保护素（OPG）的表达降低。我们得出结论，CIA大鼠发生了全身性骨质疏松，且随着CIA的发展骨质疏松变得更严重。其机制可能与DKK-1表达上调导致松质骨骨吸收增加以及RANKL/RANK/OPG信号通路的调节有关，还与DKK-1表达增加导致皮质骨骨形成减少有关。
