Immunohistochemical localization of RANK, RANKL and OPG in healthy and arthritic canine elbow joints

Abstract

Objective To determine if the receptor activator of nuclear factor-κB-receptor activator of nuclear factor-κB 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 Design Experimental study. Sample Population Fragmented 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. Methods Bright-field immunohistochemistry and high-resolution fluorescence microscopy were used to investigate the distribution of RANK, RANKL, and OPG in healthy and arthritic joints. Results All 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. Conclusions The 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 Relevance Therapeutic use of neutralizing antibodies against RANKL to inhibit osteoclast activation warrants further investigation. © 2009 by The American College of Veterinary Surgeons.