Zhu Liang, Kang Hui, Guo Chang-An, Fan Wen-Shuai, Wang Yi-Ming, Deng Lian-Fu, Yan Zuo-Qin
Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China; Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Biochem Biophys Res Commun. 2017 Feb 26;484(1):64-70. doi: 10.1016/j.bbrc.2017.01.071. Epub 2017 Jan 18.
Wear particles liberated from the surface of prostheses are considered to be main reason for osteoclast bone resorption and that extensive osteoclastogenesis leads to peri-implant osteolysis and subsequent prosthetic loosening. The aim of this study was to assess the effect of rifampin on osteoclastogenesis and titanium (Ti) particle-induced osteolysis. The Ti particle-induced osteolysis mouse calvarial model and bone marrow-derived macrophages (BMMs) were used. Rifampin, at dose of 10 or 50 mg/kg/day, was respectively given intraperitoneally for 14 days in vivo. The calvariae were removed and processed for Further histological analysis. In vitro, osteoclasts were generated from mouse BMMs with receptor activator of nuclear factor-κB ligand (RANKL) and the macrophage colony stimulating factor. Rifampin at different concentrations was added to the medium. The cell viability, tartrate-resistant acid phosphatase (TRAP) staining, TRAP activity and resorption on bone slices were analysis. Osteoclast-specific genes and RANKL-induced MAPKs signaling were tested for further study of the mechanism. Rifampin inhibited Ti-induced osteolysis and osteoclastogenesis in vivo. In vitro data indicated that rifampin suppressed osteoclast differentiation and bone resorption in a dose-dependent manner. Moreover, rifampin significantly reduced the expression of osteoclast-specific markers, including TRAP, cathepsin K, V-ATPase d2, V-ATPase a3, c-Fos, and nuclear factor of activated T cells (NFAT) c1. Further investigation revealed that rifampin inhibited osteoclast formation by specifically abrogating RANKL-induced p38 and NF-κB signaling. Rifampin had significant potential for the treatment of particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function.
从假体表面释放的磨损颗粒被认为是破骨细胞骨吸收的主要原因，广泛的破骨细胞生成会导致种植体周围骨溶解以及随后的假体松动。本研究的目的是评估利福平对破骨细胞生成和钛（Ti）颗粒诱导的骨溶解的影响。使用了Ti颗粒诱导的骨溶解小鼠颅骨模型和骨髓来源的巨噬细胞（BMMs）。利福平以10或50mg/kg/天的剂量分别在体内腹腔注射14天。取出颅骨并进行进一步的组织学分析。在体外，用核因子κB受体活化剂配体（RANKL）和巨噬细胞集落刺激因子从小鼠BMMs生成破骨细胞。将不同浓度的利福平添加到培养基中。分析细胞活力、抗酒石酸酸性磷酸酶（TRAP）染色、TRAP活性以及在骨切片上的吸收情况。检测破骨细胞特异性基因和RANKL诱导的丝裂原活化蛋白激酶（MAPKs）信号通路以进一步研究其机制。利福平在体内抑制了Ti诱导的骨溶解和破骨细胞生成。体外数据表明，利福平以剂量依赖性方式抑制破骨细胞分化和骨吸收。此外，利福平显著降低了破骨细胞特异性标志物的表达，包括TRAP、组织蛋白酶K、V-ATP酶d2、V-ATP酶a3、c-Fos和活化T细胞核因子（NFAT）c1。进一步研究表明，利福平通过特异性消除RANKL诱导的p38和NF-κB信号通路来抑制破骨细胞形成。利福平在治疗颗粒诱导的种植体周围骨溶解以及其他由破骨细胞过度形成和功能引起的疾病方面具有显著潜力。
