Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Int Immunopharmacol. 2019 Nov;76:105865. doi: 10.1016/j.intimp.2019.105865. Epub 2019 Aug 30.
Wear particle-induced periprosthetic inflammatory osteolysis and resultant aseptic loosening are major causes of orthopedic implant failure, for which there are no effective treatments other than revision surgery. Crocin, a carotenoid compound derived from crocus flowers, has anti-inflammatory properties, but its immunomodulatory function and role in particle-induced osteolysis are not well characterized. Here we report the effect of crocin on titanium (Ti) particle-induced macrophage polarization and osteogenic differentiation. We found that crocin induced anti-inflammatory (M2) macrophage polarization and attenuated Ti particle-induced inflammation by promoting the expression of anti-inflammatory cytokines in vitro as well as in vivo in a mouse air-pouch model. Additionally, crocin pre-treated macrophages promoted osteogenic differentiation of co-cultured mouse bone mesenchymal stem cells (BMSCs). These effects were mediated via inhibition of p38 and c-Jun N-terminal kinase signaling. Our results indicate that crocin suppresses Ti particle-induced inflammation and enhances osteogenic differentiation of BMSCs by inducing M2 macrophage polarization, highlighting its therapeutic potential for preventing wear particle-induced osteolysis.
磨损颗粒诱导的假体周围炎症性骨溶解和由此导致的无菌性松动是骨科植入物失效的主要原因，除了翻修手术外，目前尚无其他有效治疗方法。藏红花素是一种源自藏红花的类胡萝卜素化合物，具有抗炎特性，但它的免疫调节功能和在颗粒诱导性骨溶解中的作用尚未得到充分表征。在这里，我们报告了藏红花素对钛（Ti）颗粒诱导的巨噬细胞极化和成骨分化的影响。我们发现，藏红花素通过促进抗炎细胞因子的表达，在体外和体内（在小鼠气囊模型中）诱导抗炎（M2）巨噬细胞极化，并减轻 Ti 颗粒诱导的炎症。此外，经藏红花素预处理的巨噬细胞促进了共培养的小鼠骨髓间充质干细胞（BMSCs）的成骨分化。这些作用是通过抑制 p38 和 c-Jun N-末端激酶信号传导来介导的。我们的结果表明，藏红花素通过诱导 M2 巨噬细胞极化抑制 Ti 颗粒诱导的炎症和增强 BMSCs 的成骨分化，突出了其预防磨损颗粒诱导性骨溶解的治疗潜力。
