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Immunohistochemical Localization of RANK, RANKL and OPG in Healthy and Arthritic Canine Elbow Joints |
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| Authors: | ANDREA I SPAHNI Dr med vet PETER SCHAWALDER Prof Dr med vet BARBARA ROTHEN PD Dr sc nat ETH DIETER D BOSSHARDT PD Dr sc nat PhD NIKLAUS LANG Prof Dr med dent MICHAEL H STOFFEL Prof Dr med vet |
| Institution: | Department of Clinical Research and Veterinary Public Health, Division of Veterinary Anatomy, Department of Clinical Veterinary Medicine, the Division of Small Animal Surgery and Orthopedics, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland;;Institute of Anatomy, Medical School, University of Bern, Bern, Switzerland;and;Departments of Periodontology and Oral Surgery and Stomatology, School of Dental Medicine, University of Bern, Bern, Switzerland. |
| 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. |
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