Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, Guldhedsgatan 10A, S-41346 Göteborg, Sweden.
Bone. 2010 Mar;46(3):752-8. doi: 10.1016/j.bone.2009.10.028. Epub 2009 Oct 30.
Bacterial arthritis causes rapidly progressing joint destruction in humans. We have shown that addition of bisphosphonates or corticosteroids to conventional antimicrobial agents decreases the activity of osteoclasts, thereby reducing bone destruction. Here we assess the effect of RANKL-targeted treatments using soluble receptor decoy and osteprotegerin (OPG) on the course and outcome of staphylococcal arthritis.
Treatment was initiated 3 days after Staphylococcus aureus inoculation and included RANK-Fc, OPG-Fc, and OPG-Fc in combination with antibiotics. Control groups were treated with antibiotics, huFc, and PBS. Joints were evaluated for clinical signs of arthritis and histologically for bone and cartilage destruction. Bone mineral density (BMD) was evaluated using a peripheral quantitative computed tomography. Circulating markers of bone metabolism, inflammatory cytokines, and chemokines were analyzed in each group.
Mice treated with RANK-Fc or OPG-Fc in combination with antibiotics preserved total BMD and trabecular bone as compared to huFc or antibiotics. Treatment with RANK-Fc or OPG-Fc diminished the levels of bone resorption markers (osteocalcin, CTX-I, and TRACP5b). Neither RANK-Fc nor OPG-Fc influenced significantly the frequency and severity of arthritis.
Inhibition of RANKL signalling efficiently prevents bone loss in the mouse model of bacterial arthritis even when started in the overt phase of infection.
细菌性关节炎会导致人类关节迅速破坏。我们已经证明，在常规抗菌药物中添加双膦酸盐或皮质类固醇可以降低破骨细胞的活性，从而减少骨质破坏。在此，我们评估了使用可溶性受体诱饵和护骨素（OPG）对金黄色葡萄球菌关节炎病程和结局的影响。
在金黄色葡萄球菌接种后 3 天开始治疗，包括 RANK-Fc、OPG-Fc 和 OPG-Fc 联合抗生素。对照组接受抗生素、huFc 和 PBS 治疗。评估关节的关节炎临床症状和组织学的骨和软骨破坏情况。使用外周定量计算机断层扫描评估骨矿物质密度（BMD）。分析各组循环骨代谢标志物、炎症细胞因子和趋化因子。
与 huFc 或抗生素相比，用 RANK-Fc 或 OPG-Fc 联合抗生素治疗的小鼠保留了总 BMD 和小梁骨。用 RANK-Fc 或 OPG-Fc 治疗可降低骨吸收标志物（骨钙素、CTX-I 和 TRACP5b）的水平。RANK-Fc 或 OPG-Fc 均未显著影响关节炎的频率和严重程度。
即使在感染的明显阶段开始，抑制 RANKL 信号也能有效防止细菌性关节炎小鼠模型的骨质流失。
