title: Nitric oxide synthase I mediates osteoclast activity in vitro and in vivo.
abstract: Bone resorption is responsible for the morbidity associated with a number of inflammatory diseases such as rheumatoid arthritis, orthopedic implant osteolysis, periodontitis and aural cholesteatoma. Previous studies have established nitric oxide (NO) as a potentially important mediator of bone resorption. NO is a unique intercellular and intracellular signaling molecule involved in many physiologic and pathologic pathways. NO is generated from L-arginine by the enzyme nitric oxide synthase (NOS). There are three known isoforms of NOS with distinct cellular distributions. In this study, we have used mice with targeted deletions in each of these isoforms to establish a role for these enzymes in the regulation of bone resorption in vivo and in vitro. In a murine model of particle induced osteolysis, NOS I-/- mice demonstrated a significantly reduced osteoclast response. In vitro, osteoclasts derived from NOS I-/- mice were larger than wild type controls but demonstrated decreased resorption. Although NOS I has been demonstrated in osteoblasts and osteocytes as a mediator of adaptive bone remodeling, it has not previously been identified in osteoclasts. These results demonstrate a critical role for NOS I in inflammatory bone resorption and osteoclast function in vitro.
authors.affiliation: Department of Otolaryngology, Washington University, St Louis, Missouri 63110, USA.
authors.forename: Jae Y
authors.initials: JY
authors.lastname: Jung
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Lin
authors.forename: Lisette M
authors.initials: LM
authors.lastname: Ramos
authors.forename: Brian T
authors.initials: BT
authors.lastname: Faddis
authors.forename: Richard A
authors.initials: RA
authors.lastname: Chole
mesh_terms: D000818:Animals; D001483:Base Sequence; D001862:Bone Resorption; D017931:DNA Primers; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D010006:Osteoblasts / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D019001:Nitric Oxide Synthase