Immunohistochemical Localization of RANK, RANKL and OPG in Healthy and Arthritic Canine Elbow Joints
Immunohistochemical Localization of RANK, RANKL and OPG in Healthy and Arthritic Canine Elbow Joints
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DOI：
10.1111/j.1532-950x.2009.00566.x
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发表时间：
2009-08-01
影响因子：
1.8
通讯作者：
Stoffel, Michael H.
中科院分区：
文献类型：
--
作者：
Spahni, Andrea I.;Schawalder, Peter;Stoffel, Michael H.
目的探讨核因子- κ B受体激活剂配体-骨保护素（RANK-RANKL-OPG）系统在犬骨重塑中是否有活性，如果有活性，这些介质在健康关节和关节炎关节中的表达是否存在差异。研究设计：实验研究。从患肘关节关节炎的狗身上手术切除碎片状冠突（n=20），从因肘关节疾病以外的原因安乐死的狗身上手术切除5个相应的健康样本。方法采用亮场免疫组织化学和高分辨率荧光显微镜观察正常关节和关节炎关节中RANK、RANKL和OPG的分布。结果犬骨组织免疫染色均鉴定出3个分子。肘关节发育不良时，rank阳性破骨细胞数量增加。在它们附近，表达RANKL（一种破骨细胞活化介质）的细胞数量丰富，而通过OPG限制破骨细胞发生和骨吸收的成骨细胞数量很少。结论RANK-RANKL-OPG系统在犬骨重塑中具有活性。在肘关节发育不良中，促进破骨细胞发生的分子过剩是明显的，这表明调节骨吸收和骨形成的介质之间存在不平衡。OPG和抗RANKL的中和抗体都具有平衡骨吸收的潜力。临床意义治疗中使用抗RANKL的中和抗体来抑制破骨细胞的活化值得进一步研究。
ObjectiveTo determine if the receptor activator of nuclear factor-kappa B-receptor activator of nuclear factor-kappa B ligand-osteoprotegerin (RANK-RANKL-OPG) system is active in bone remodeling in dogs and, if so, whether differences in expression of these mediators occur in healthy and arthritic joints.Study DesignExperimental study.Sample PopulationFragmented processus coronoidei (n=20) were surgically removed from dogs with elbow arthritis and 5 corresponding healthy samples from dogs euthanatized for reasons other than elbow joint disease.MethodsBright-field immunohistochemistry and high-resolution fluorescence microscopy were used to investigate the distribution of RANK, RANKL, and OPG in healthy and arthritic joints.ResultsAll 3 molecules were identified by immunostaining of canine bone tissue. In elbow dysplasia, the number of RANK-positive osteoclasts was increased. In their vicinity, cells expressing RANKL, a mediator of osteoclast activation, were abundant whereas the number of osteoblasts having the potential to limit osteoclastogenesis and bone resorption via OPG was few.ConclusionsThe RANK-RANKL-OPG system is active in bone remodeling in dogs. In elbow dysplasia, a surplus of molecules promoting osteoclastogenesis was evident and is indicative of an imbalance between the mediators regulating bone resorption and bone formation. Both OPG and neutralizing antibodies against RANKL have the potential to counterbalance bone resorption.Clinical RelevanceTherapeutic use of neutralizing antibodies against RANKL to inhibit osteoclast activation warrants further investigation.