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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.

Abstract

OBJECTIVE

Bone metabolism in spondyloarthritis (SpA) is not well elucidated. We investigated alterations in bone in the HLA-B27 transgenic rat, a model of SpA.

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-kappa B 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.

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  • Authors+Show Affiliations

    ,

    Institute of Pathophysiology, Medical University of Vienna, Vienna, Austria. martina.rauner@uniklinikum-dresden.de

    , , , , , ,

    Source

    The Journal of rheumatology 36:1 2009 Jan pg 120-6

    MeSH

    Animals
    Biomarkers
    Bone Density
    Disease Models, Animal
    Female
    Gene Expression
    HLA-B27 Antigen
    Humans
    Male
    Osteoporosis
    Osteoprotegerin
    RANK Ligand
    RNA, Messenger
    Rats
    Rats, Inbred F344
    Rats, Transgenic
    Spondylarthritis

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    19040304