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Nitric oxide synthase I mediates osteoclast activity in vitro and in vivo
Author(s) -
Jung Jae Y.,
Lin Aaron C.,
Ramos Lisette M.,
Faddis Brian T.,
Chole Richard A.
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10527
Subject(s) - bone resorption , osteoclast , nitric oxide synthase , osteolysis , nitric oxide , chemistry , in vivo , resorption , microbiology and biotechnology , osteoblast , bone remodeling , in vitro , medicine , endocrinology , biology , biochemistry , dentistry
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. © 2003 Wiley‐Liss, Inc.