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The HLA-B27 Transgenic Rat, a Model of Spondyloarthritis, Has Decreased Bone Mineral Density and Increased RANKL to Osteoprotegerin mRNA Ratio MARTINA RAUNER, DANIELA STUPPHANN, MARTIN HAAS, INGRID FERT, SIMON GLATIGNY, WOLFGANG SIPOS, MAXIME BREBAN, and PETER PIETSCHMANN
ABSTRACT. Methods. Femur, tibia, and lumbar vertebral bodies of disease-prone HLA-B27 transgenic, healthy HLA-B7 transgenic, and nontransgenic control rats were used for bone histomorphometric and dual energy x-ray absorptiometry (DEXA) analysis. Serum levels of type I collagen C-telopeptides (CTX), N-terminal propeptide of type I procollagen (P1NP), and osteocalcin, as well as receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG), were measured. RNA was isolated from the bone tissue of the femura to analyze gene expression of RANKL, OPG, and osteocalcin. Results. Histomorphometric analysis indicated a significant decrease in bone volume as well as trabecular number and thickness in the HLA-B27 rats. Trabecular separation was increased. Numbers of osteoblasts, osteoclasts, and osteoid volume were not altered significantly. The decrease in bone mineral density was confirmed using DEXA. Levels of RANKL mRNA were significantly increased in the bone tissue of HLA-B27 transgenic rats, resulting in an increased RANKL to OPG ratio. Osteocalcin mRNA expression was also significantly elevated in bone of HLA-B27 rats. Serum levels of CTX, RANKL, OPG, P1NP, and osteocalcin did not differ significantly. Conclusion. Our data indicate that, similarly to SpA in humans, HLA-B27 transgenic rats show a reduced bone mass, and suggest an involvement of the RANKL/OPG system in the mechanism of bone loss in this disease. This model may be adequate to study osteoporosis in SpA. (J Rheumatol First Release Dec 1 2008; doi 10.3899/jrheum.080475) Key Indexing Terms:
SPONDYLOARTHROPATHY From the Institute of Pathophysiology, Medical University of Vienna, Vienna, Austria; Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine III, Technical University of Dresden, Dresden, Germany; Internal Medicine III, Department of Nephrology, Medical University of Vienna, Vienna, Austria; Institut Cochin, Hôpital Cochin, Paris, France; and Medical Clinic II, University of Veterinary Medicine, Vienna, Austria. Supported by a travel grant from the Austrian Bone and Mineral Society to M. Rauner and D. Stupphann. M. Rauner, Institute of Pathophysiology, Medical University of Vienna, Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine III, Technical University of Dresden; D. Stupphann, MSc, Institute of Pathophysiology, Medical University of Vienna; M. Haas, MD, Internal Medicine III, Department of Nephrology, Medical University of Vienna; I. Fert, BSc; S. Glatigny, MSc, Institut Cochin, Hôpital Cochin; W. Sipos, DVM, Medical Clinic II, University of Veterinary Medicine, Vienna; M. Breban, MD, PhD, Institut Cochin, Hôpital Cochin; P. Pietschmann, MD, Institute of Pathophysiology, Medical University of Vienna. M. Rauner and D. Stupphann contributed equally to this report. Address reprint requests to M. Rauner, Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Medical Faculty of Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. E-mail: martina.rauner@uniklinikum-dresden.de Accepted for publication August 18, 2008.
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