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Osteoclasts; culprits in inflammatory osteolysis

Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8118, St Louis, MO 63110, USA.
Arthritis research & therapy (Impact Factor: 4.12). 02/2006; 8(1):201. DOI: 10.1186/ar1857
Source: PubMed

ABSTRACT Periarticular osteolysis, a crippling complication of rheumatoid arthritis, is the product of enhanced osteoclast recruitment and activation. The osteoclast, which is a member of the monocyte/macrophage family, is the exclusive bone resorptive cell, and its differentiation and activation are under the aegis of a variety of cytokines. Receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor are the essential osteoclastogenic cytokines and are increased in inflammatory joint disease. Tumor necrosis factor-alpha, which perpetrates arthritic bone loss, exerts its osteoclastogenic effect in the context of RANKL with which it synergizes. Achieving an understanding of the mechanisms by which the three cytokines affect the osteoclast has resulted in a number of active and candidate therapeutic targets.

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Available from: Steven Teitelbaum, Sep 22, 2014
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    • "3–5). RANKL is a soluble, osteoblast-derived protein that induces bone resorption through osteoclast differentiation and activation (Teitelbaum, 2006). RANKL expression is induced in osteoblasts/ mesenchymal cells by a bone resorption factor (Yasuda et al., 1998). "
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    ABSTRACT: Bone diseases are characterized by the presence of pro-inflammatory cytokines that regulate bone turnover. The receptor activator of NF-κB ligand (RANKL) is a soluble osteoblast-derived protein that induces bone resorption through osteoclast differentiation and activation. Sargachromanol G (SG) was isolated from the brown algae Sargassum siliquastrum; SG has anti-osteoclastogenic activity, but its mechanism of action and its active components remain largely unknown. In the present study, we investigated the anti-osteoclastogenic effects of SG on the expression of interleukin-1β (IL-1β)-induced osteoclastogenic factors (PGE(2), COX-2, IL-6, OPG, and RANKL) in the human osteoblast cell line MG-63. We also examined the role of the nuclear factor-κB (NF-κB) and the mitogen-activated protein kinase (MAPK) signaling pathways in IL-1β-stimulated MG-63 cells. SG dose-dependently inhibited the production of osteoclastogenic factors in MG-63 cells. SG also inhibited phosphorylation of MAPK (ERK1/2, p38, and JNK) and NF-κB (p65, p50, and IκB-α). These results suggest that the anti-osteoporotic effect of SG may be because of the modulation of osteoclastogenic factors via suppression of MAPK and NF-κB activation.
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    • "Osteoclastogenesis is modulated by various factors, most of which mediate their effects primarily via osteoblasts [34]. The two essential factors required for osteoclast differentiation are receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony stimulating factor-1 (M-CSF) [34] [35] [36]. Osteoclasts have distinct membrane domains. "
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