title: Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis.
abstract: 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.
authors.affiliation: Microscopy and Imaging Core Facility, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Rewati
authors.initials: R
authors.lastname: Adhikari
authors.affiliation: National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Yamada
authors.affiliation: Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA. Electronic address: subhash.dhawan@fda.hhs.gov.
authors.forename: Subhash
authors.initials: S
authors.lastname: Dhawan
mesh_terms: D002454:Cell Differentiation; D017277:Drug Approval; D058492:Drug Repositioning; D004790:Enzyme Induction / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006427:Hemin / Q000494:pharmacology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D010010:Osteoclasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D061251:Primary Cell Culture
chemical_list: D006427:Hemin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: HIV-1; Heme oxygenase-1; Hemin; Osteoclasts