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Title: Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis

The normal skeletal developmental and homeostatic process termed osteoclastogenesis is exacerbated in numerous pathological conditions and causes excess bone loss. In cancer and HIV-1-infected patients, this disruption of homeostasis results in osteopenia and eventual osteoporesis. Counteracting the factors responsible for these metabolic disorders remains a challenge for preventing or minimizing this co-morbidity associated with these diseases. In this report, we demonstrate that a hemin-induced host protection mechanism not only suppresses HIV-1 associated osteoclastogenesis, but it also exhibits anti-osteoclastogenic activity for non-infected cells. Since the mode of action of hemin is both physiological and pharmacological through induction of heme oxygenase-1 (HO-1), an endogenous host protective response to an FDA-licensed therapeutic used to treat another disease, our study suggests an approach to developing novel, safe and effective therapeutic strategies for treating bone disorders, because hemin administration in humans has previously met required FDA safety standards. - Highlights: • HIV-1 infection induced osteoclastogenesis in primary human macrophages. • Heme oxygenase-1 (HO-1) induction inhibited HIV-1-induced osteoclastogenesis in macrophages. • HO-1 induction suppressed RANKL-enhanced osteoclastogenesis in HIV-1-infected macrophages. • This inverse relationship between HO-1 and HIV-1 pathogenesis may define a novel host defense response against HIV-1 infection.
Authors:
 [1] ;  [2] ;  [3] ;  [2]
  1. Microscopy and Imaging Core Facility, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD (United States)
  2. Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)
  3. National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)
Publication Date:
OSTI Identifier:
22462172
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 464; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIDS VIRUS; DISEASE INCIDENCE; HEME; HOMEOSTASIS; HOST; HUMAN POPULATIONS; LICENSES; MACROPHAGES; NEOPLASMS; PATHOGENESIS; PATIENTS; SAFETY; SAFETY STANDARDS; SKELETON