Zhao Shuai, Sun Yu, Li Xiaolei, Wang Jingcheng, Yan Lianqi, Zhang Zhen, Wang Daxin, Dai Jihang, He Jun, Wang Shuguang
Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan 410012, China.
Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
Int Immunopharmacol. 2016 Nov;40:458-465. doi: 10.1016/j.intimp.2016.09.031. Epub 2016 Oct 8.
Aseptic prosthetic loosening is a major complication after hip joint replacement. Wear particle-induced periprosthetic osteolysis plays a key role in aseptic prosthetic loosening. Attempting to modulate receptor activator of nuclear factor-κB (RANKL) mediated signaling pathways is a promising strategy to prevent aseptic prosthetic loosening. In the present study, we determined the effect of scutellarin (SCU) on titanium (Ti) particle-induced osteolysis in a mouse calvarial model and RANKL-mediated osteoclastogenesis. We determined that SCU, the major effective constituent of breviscapine isolated from a Chinese herb, has potential effects on preventing Ti particle-caused osteolysis in calvarial model of mouse. In vitro, SCU could suppress RANKL-mediated osteoclastogenesis, the function of osteoclast bone resorption, and the expression levels of osteoclast-specific genes (tartrate-resistant acid phosphatase (TRAP), cathepsin K, c-Fos, NFATc1). Further investigation indicated that SCU could inhibit RANKL-mediated MAPK and NF-κB signaling pathway, including JNK1/2, p38, ERK1/2, and IκBα phosphorylation. Taken together, these results indicate that SCU could inhibit osteoclastogenesis and prevent Ti particle-induced osteolysis by suppressing RANKL-mediated MAPK and NF-κB signaling pathway. These results suggest that SCU is a promising therapeutic agent for preventing wear particle-induced periprosthetic osteolysis.
无菌性假体松动是髋关节置换术后的主要并发症。磨损颗粒诱导的假体周围骨溶解在无菌性假体松动中起关键作用。试图调节核因子κB受体激活剂（RANKL）介导的信号通路是预防无菌性假体松动的一种有前景的策略。在本研究中，我们在小鼠颅骨模型中确定了灯盏花素（SCU）对钛（Ti）颗粒诱导的骨溶解以及RANKL介导的破骨细胞生成的影响。我们确定，从一种中草药中分离出的灯盏细辛的主要有效成分SCU，在小鼠颅骨模型中对预防Ti颗粒引起的骨溶解具有潜在作用。在体外，SCU可以抑制RANKL介导的破骨细胞生成、破骨细胞骨吸收功能以及破骨细胞特异性基因（抗酒石酸酸性磷酸酶（TRAP）、组织蛋白酶K、c-Fos、NFATc1）的表达水平。进一步研究表明，SCU可以抑制RANKL介导的MAPK和NF-κB信号通路，包括JNK1/2、p38、ERK1/2和IκBα磷酸化。综上所述，这些结果表明SCU可以通过抑制RANKL介导的MAPK和NF-κB信号通路来抑制破骨细胞生成并预防Ti颗粒诱导的骨溶解。这些结果表明，SCU是预防磨损颗粒诱导的假体周围骨溶解的一种有前景的治疗药物。
