Bacteria induce osteoclastogenesis via an osteoblast-independent pathway
Date
2002
DOI
Authors
Mehta, Chetan K.
Version
OA Version
Citation
Abstract
Bacteria or their products may cause chronic inflammation and subsequent bone loss. This inflammation and bone loss may be associated with significant morbidity in chronic otitis media, periodontitis, endodontic lesions, and loosening of orthopedic implants caused by lipopolysaccharide (LPS)-contaminated implant particles. Currently, it is not clear how bacteria or endotoxin-induced bone resorption occurs and what cell types are involved.
The aim of this study was to determine if Porphyromonas gingivalis, a periodontal pathogen, Porphyromonas endodontalis, an endodontic pathogen, and Escherichia coli LPS induce osteoclastic cell formation from murine leukocytes in the absence of osteoblasts. The formation of resorbing cells was measured directly from precursors in splenic cell cultures by the induction of multinuclear tartrate-resistant acid phosphatase (TRAP) positive cells and by formation of resorption pits on dentin slices. P. gingivalis, P. endodontalis and E. coli LPS induced osteoclast formation from murine leukocytes in a dose-dependent manner. When stimulated with 10 [4] or more bacteria, a statistically significant increase in TRAP was observed compared to untreated control cells (Student’s t-test; p [less than]0.05). These cells were capable of resorbing dentin surfaces. In contrast, stimulation with parathyroid hormone had no effect. These multinucleated, tartrate-resistant acid phosphatase-positive cells were positive for receptor activator of NF-KB (RANK), the receptor for osteoprotegerin ligand (OPGL), also known as RANK ligand (RANKL). Blocking antibodies demonstrated that their formation was dependent upon expression of OPGL and, to a lesser extent, on tumor necrosis factor alpha. Mononuclear cells represented a significant source of OPGL production. These findings describe a pathway by which bacteria could enhance osteolysis independently of osteoblasts and suggest that the mix of cells that participate in inflammatory and physiologic bone resorption may be different. This may give insight into new targets of therapeutic intervention.
Description
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Thesis (M.Sc.D.)--Boston University, Henry M. Goldman School of Dental Medicine, 2002 (Endodontics).
Includes bibliographic references (leaves 63-71).
Thesis (M.Sc.D.)--Boston University, Henry M. Goldman School of Dental Medicine, 2002 (Endodontics).
Includes bibliographic references (leaves 63-71).
License
This work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.