title: Bacteria induce osteoclastogenesis via an osteoblast-independent pathway.
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. Here we report that Porphyromonas gingivalis, a periodontal pathogen, and Escherichia coli LPS induce osteoclastic cell formation from murine leukocytes in the absence of osteoblasts. In contrast, stimulation with parathyroid hormone had no effect. These multinucleated, tartrate-resistant acid phosphatase-positive cells were positive for receptor activator of NF-kappaB (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. In vivo, P. gingivalis injection stimulated OPGL expression in both mononuclear leukocytes and osteoblastic cells. Thus, 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.
authors: Department of Endodontics, Boston University School of Dental Medicine, Boston, Massachusetts 02118, USA. yljiang@bu.edu
authors: Yanling
authors: Y
authors: Jiang
authors: Chetan K
authors: CK
authors: Mehta
authors: Tun-Yi
authors: TY
authors: Hsu
authors: Fahad F H
authors: FF
authors: Alsulaimani
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D015415:Biomarkers; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D006023:Glycoproteins / Q000032:analysis; D007527:Isoenzymes / Q000032:analysis; D007962:Leukocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology*; D010012:Osteogenesis / Q000276:immunology*; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000494:pharmacology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor; D013154:Spleen / Q000166:cytology; D000071681:Tartrate-Resistant Acid Phosphatase; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase