Rhoifolin ameliorates titanium particle-stimulated osteolysis and attenuates osteoclastogenesis via RANKL-induced NF-κB and MAPK pathways
Rhoifolin ameliorates titanium particle-stimulated osteolysis and attenuates osteoclastogenesis via RANKL-induced NF-κB and MAPK pathways
复制标题
Rhoifolin 通过 RANKL 诱导的 NF-kappa B 和 MAPK 途径改善钛颗粒刺激的骨质溶解并减弱破骨细胞生成
DOI：
10.1002/jcp.28384
复制
发表时间：
2019-10-01
影响因子：
5.6
通讯作者：
Liu, Qian
中科院分区：
文献类型：
--
作者：
Liao, Shijie;Song, Fangmin;Liu, Qian
假体松动是全关节置换术后的一个非常棘手的临床问题。磨损颗粒诱导的破骨细胞生成已被证明是假体周围骨质溶解的主要原因，最终导致假体无菌性松动。因此，抑制破骨细胞生成是控制假体周围骨溶解的一个有前途的策略。在这项研究中，rhoifolin对破骨细胞生成和钛颗粒诱导的颅骨骨溶解的可能作用机制进行了研究。体外实验表明，野漆树素能强烈抑制核因子-κ B（NF-κ B）受体激活剂配体刺激的破骨细胞生成、羟基磷灰石吸收、F-肌动蛋白形成以及破骨细胞相关基因的基因表达。Western blot分析表明，野漆树苷可抑制NF-κ B和丝裂原活化蛋白激酶通路，抑制活化T细胞核因子1（NFATc 1）和c-Fos的表达。进一步的研究表明，rhoifolin抑制p65向细胞核的转位，NFATc 1和NF-κ B的活性可以减少体内抗酒石酸酸性磷酸盐阳性破骨细胞的数量和钛颗粒诱导的C57小鼠颅骨骨丢失。综上所述，我们的研究结果表明，rhoifolin可以改善破骨细胞刺激的骨溶解，并可能是一个潜在的治疗假体松动的药物。
Prosthesis loosening is a highly troublesome clinical problem following total joint arthroplasty. Wear-particle-induced osteoclastogenesis has been shown to be the primary cause of periprosthetic osteolysis that eventually leads to aseptic prosthesis loosening. Therefore, inhibiting osteoclastogenesis is a promising strategy to control periprosthetic osteolysis. The possible mechanism of action of rhoifolin on osteoclastogenesis and titanium particle-induced calvarial osteolysis was examined in this study. The in vitro study showed that rhoifolin could strongly suppress the receptor activators of nuclear factor-kappa B (NF-kappa B) ligand-stimulated osteoclastogenesis, hydroxyapatite resorption, F-actin formation, and the gene expression of osteoclast-related genes. Western blot analysis illustrated that rhoifolin could attenuate the NF-kappa B and mitogen-activated protein kinase pathways, and the expression of transcriptional factors nuclear factor of activated T cells 1 (NFATc1) and c-Fos. Further studies indicated that rhoifolin inhibited p65 translocation to the nucleus and the activity of NFATc1 and NF-kappa B rhoifolin could decrease the number of tartrate-resistant acid phosphate-positive osteoclasts and titanium particle-induced C57 mouse calvarial bone loss in vivo. In conclusion, our results suggest that rhoifolin can ameliorate the osteoclasts-stimulated osteolysis, and may be a potential agent for the treatment of prosthesis loosening.