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

Proceedings of the National Academy of Sciences of the United States of America
Tatyana VikulinaM Neale Weitzmann

Abstract

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 ...Continue Reading

Associated Clinical Trials

Oct 26, 2010·Ighovwerha Ofotokun, Ighovwerha Ofotokun

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Citations

Apr 3, 2013·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Xiaosha PangLinda Chang
Dec 20, 2011·Current HIV/AIDS Reports·Ighovwerha OfotokunM Neale Weitzmann
Oct 27, 2012·Current Osteoporosis Reports·Micol S Rothman, Mary T Bessesen
Jul 24, 2012·Current Opinion in Rheumatology·Lydia Gedmintas, Daniel H Solomon
Sep 17, 2010·Current Opinion in Endocrinology, Diabetes, and Obesity·Ighovwerha Ofotokun, M Neale Weitzmann
Oct 4, 2012·AIDS·Linda A DiMeglioUNKNOWN Pediatric HIVAIDS Cohort Study (PHACS)
Apr 18, 2013·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Todd T BrownGrace A McComsey
Jun 9, 2012·Skeletal Muscle·Rebecca L KuskoMonty Montano
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Jun 21, 2013·Journal of the International AIDS Society·Thanyawee Puthanakit, George K Siberry
Sep 6, 2014·Current Opinion in Endocrinology, Diabetes, and Obesity·M Neale Weitzmann
Feb 15, 2014·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Kristine M ErlandsonGrace A McComsey
Jan 15, 2014·Current HIV/AIDS Reports·Anna C HearpsSuzanne M Crowe
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Dec 18, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Shin-Woo HaGeorge R Beck
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Mar 3, 2018·Proceedings of the National Academy of Sciences of the United States of America·Ighovwerha Ofotokun
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Sep 24, 2015·Nature Communications·Ighovwerha OfotokunM Neale Weitzmann
Jul 4, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Janaina RamalhoRosa Ma Moyses
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