RGD Reference Report - Alterations in the immuno-skeletal interface drive bone destruction in HIV-1 transgenic rats. - Rat Genome Database

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Alterations in the immuno-skeletal interface drive bone destruction in HIV-1 transgenic rats.

Authors: Vikulina, Tatyana  Fan, Xian  Yamaguchi, Masayoshi  Roser-Page, Susanne  Zayzafoon, Majd  Guidot, David M  Ofotokun, Ighovwerha  Weitzmann, M Neale 
Citation: Vikulina T, etal., Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13848-53. doi: 10.1073/pnas.1003020107. Epub 2010 Jul 19.
RGD ID: 42722617
Pubmed: (View Article at PubMed) PMID:20643942
DOI: Full-text: DOI:10.1073/pnas.1003020107

Osteoporosis and bone fractures are increasingly recognized complications of HIV-1 infection. Although antiretroviral therapy itself has complex effects on bone turnover, it is now evident that the majority of HIV-infected individuals already exhibit reduced bone mineral density before therapy. The mechanisms responsible are likely multifactorial and have been difficult to delineate in humans. The HIV-1 transgenic rat recapitulates many key features of human AIDS. We now demonstrate that, like their human counterparts, HIV-1 transgenic rats undergo severe osteoclastic bone resorption, a consequence of an imbalance in the ratio of receptor activator of NF-kappaB ligand, the key osteoclastogenic cytokine, to that of its physiological decoy receptor osteoprotegerin. This imbalance stemmed from a switch in production of osteoprotegerin to that of receptor activator of NF-kappaB ligand by B cells, and was further compounded by a significantly elevated number of osteoclast precursors. With the advancing age of individuals living with HIV/AIDS, low bone mineral density associated with HIV infection is likely to collide with the pathophysiology of skeletal aging, leading to increased fracture risk. Understanding the mechanisms driving bone loss in HIV-infected individuals will be critical to developing effective therapeutic strategies.



Objects Annotated

Strains
F344-Tg(HIV)1Hsd  (NA)


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