Li Yamin, Li Juehong, Li Bin, Qin Hui, Peng Xiaochun, Zhao Yaochao, Chen Yunsu
Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 7th Floor Orthopaedic Department, No. 6 Building, No. 600 Yishan Road, Shanghai, China.
Mol Immunol. 2017 May;85:27-34. doi: 10.1016/j.molimm.2017.02.003. Epub 2017 Feb 14.
Wear particle-induced osteolysis and bone resorption have been identified as critical factors of implant failure and total joint revision, in which nuclear factor kappa B (NF-κB) signaling and chronic inflammation have been shown to play key roles. Although anthocyanin is known to have anti-inflammatory function via blocking NF-κB pathway, it is still unclear whether anthocyanin has a protective effect on particle-induced osteolysis. In the present study, we aimed to investigate the detailed effects and the underlying mechanism of anthocyanin on CoCrMo particle-induced osteolysis in a mouse calvavial model. One hundred and twelve male BALB/c mice were divided randomly into four groups: sham group (sham operation and injection with PBS), vehicle group (CoCrMo particle treatment and injection with PBS), low-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.1mg/g/day), and high-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.4mg/g/day). Mice were sacrificed after two weeks, harvesting the calvariae tissue for in depth analysis by micro-CT, histomorphometry, immunohistochemical and molecular biology analysis. As expected, anthocyanin markedly inhibited CoCrMo particle-induced inflammatory infiltration and decreased bone loss in vivo. Anthocyanin also reversed the increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL)/osteoproteger (OPG) and suppressed osteoclast formation in CoCrMo particle-stimulated calvaria. Additionally, anthocyanin significantly reduced the expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the calvaria of CoCrMo-stimulated mice. Furthermore, we confirmed that anthocyanin attenuated osteolysis by blocking NF-κB pathway via inhibiting inhibitor of nuclear factor kappa-B kinase α/β (IKKα/β) phosphorylation. In conclusion, our study demonstrated that anthocyanin can protect against CoCrMo particle-induced inflammatory osteolysis via inhibiting the IKKα/β-NF-κB pathway, and have a potential therapeutic effect on the treatment of wear particle-induced osteolysis.
磨损颗粒诱导的骨溶解和骨吸收已被确定为植入物失败和全关节翻修的关键因素，其中核因子κB（NF-κB）信号传导和慢性炎症已被证明起关键作用。尽管已知花青素通过阻断NF-κB途径具有抗炎功能，但花青素是否对颗粒诱导的骨溶解具有保护作用仍不清楚。在本研究中，我们旨在研究花青素对小鼠颅骨模型中CoCrMo颗粒诱导的骨溶解的详细影响及其潜在机制。112只雄性BALB/c小鼠随机分为四组：假手术组（假手术并注射PBS）、载体组（CoCrMo颗粒处理并注射PBS）、低剂量花青素组（CoCrMo颗粒处理并以0.1mg/g/天注射花青素）和高剂量花青素组（CoCrMo颗粒处理并以0.4mg/g/天注射花青素）。两周后处死小鼠，收集颅骨组织进行微CT、组织形态计量学、免疫组织化学和分子生物学分析以进行深入研究。正如预期的那样，花青素在体内显著抑制CoCrMo颗粒诱导的炎症浸润并减少骨质流失。花青素还逆转了核因子κB受体激活剂配体（RANKL）/骨保护素（OPG）比值的增加，并抑制了CoCrMo颗粒刺激的颅骨中的破骨细胞形成。此外，花青素显著降低了CoCrMo刺激的小鼠颅骨中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的表达和分泌。此外，我们证实花青素通过抑制核因子κB激酶α/β（IKKα/β）磷酸化来阻断NF-κB途径，从而减轻骨溶解。总之，我们的研究表明，花青素可以通过抑制IKKα/β-NF-κB途径来预防CoCrMo颗粒诱导的炎症性骨溶解，并且对磨损颗粒诱导的骨溶解的治疗具有潜在疗效。
