von Knoch Fabian, Heckelei Anja, Wedemeyer Christian, Saxler Guido, Hilken Gero, Brankamp Jochen, Sterner Thomas, Landgraeber Stefan, Henschke Frank, Löer Franz, von Knoch Marius
Department of Orthopaedic Surgery, Kantonsspital Chur, Loestrasse 170, 7000 Chur, Switzerland.
J Biomed Mater Res A. 2005 Nov 1;75(2):288-94. doi: 10.1002/jbm.a.30441.
Alterations of the key regulators of osteoclastogenesis, receptor activator of NF-kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) have been implicated in wear particle-induced osteolysis, the most common cause for implant failure in total joint replacements. This study investigated the effect of exogenous OPG on ultra-high-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was utilized in 28 C57BL/6J mice randomized to four groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III and IV particles and subcutaneous OPG starting from day 0 (group III) or day 5 (group IV) until sacrifice. After 2 weeks, calvaria were prepared for histology and histomorphometry. Bone resorption was measured within the midline suture using Giemsa staining and osteoclast numbers were determined using TRAP staining. UHMWPE particle implantation resulted in grossly pronounced osteoclastogenesis and bone resorption. Both immediate and delayed treatment with OPG counteracted these particle-induced effects significantly, suppressing osteoclast formation and bone resorption (p < 0.001 and p < 0.001, respectively). In conclusion, exogenous OPG markedly suppressed UHMWPE particle-induced osteolysis in a murine calvarial model. This important finding underscores the crucial significance of the OPG-RANKL-RANK signaling in wear particle-induced osteolysis. Exogenous OPG may prove an effective treatment modality for wear debris-mediated periprosthetic osteolysis after total joint arthroplasty.
破骨细胞生成的关键调节因子，即核因子κB受体活化因子（RANK）、RANK配体（RANKL）和骨保护素（OPG）的改变与磨损颗粒诱导的骨溶解有关，而骨溶解是全关节置换中植入失败的最常见原因。本研究调查了外源性OPG对超高分子量聚乙烯（UHMWPE）颗粒诱导的骨溶解的影响。在28只C57BL/6J小鼠中采用小鼠颅骨骨溶解模型，并将其随机分为四组。第一组仅接受假手术，第二组接受UHMWPE颗粒，第三组和第四组从第0天（第三组）或第5天（第四组）开始接受颗粒和皮下注射OPG，直至处死。2周后，制备颅骨用于组织学和组织形态计量学分析。使用吉姆萨染色测量中线缝合处的骨吸收情况，并使用抗酒石酸酸性磷酸酶（TRAP）染色确定破骨细胞数量。UHMWPE颗粒植入导致明显的破骨细胞生成和骨吸收。OPG的即时和延迟治疗均显著抵消了这些颗粒诱导的效应，抑制了破骨细胞形成和骨吸收（分别为p < 0.001和p < 0.001）。总之，在小鼠颅骨模型中，外源性OPG显著抑制了UHMWPE颗粒诱导的骨溶解。这一重要发现强调了OPG-RANKL-RANK信号在磨损颗粒诱导的骨溶解中的关键意义。外源性OPG可能被证明是全关节置换术后磨损碎屑介导的假体周围骨溶解的一种有效治疗方式。
