𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through interaction with receptor activator of nuclear factor κB, osteoprotegerin, and receptor activator of nuclear factor κB ligand

✍ Scribed by Chang-Keun Lee; Eun Young Lee; Son Mi Chung; Se Hwan Mun; Bin Yoo; Hee-Bom Moon

Publisher
John Wiley and Sons
Year
2004
Tongue
English
Weight
649 KB
Volume
50
Category
Article
ISSN
0004-3591

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Objective

To demonstrate the effects of disease‐modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through their effects on receptor activator of nuclear factor κB (RANK), osteoprotegerin (OPG), and RANK ligand (RANKL).

Methods

Peripheral blood mononuclear cells (PBMCs) and rheumatoid arthritis (RA) fibroblast‐like synoviocytes (FLS) were cocultured in the presence of macrophage colony‐stimulating factor, 1,25‐dihydroxyvitamin D~3~, and various concentrations of methotrexate (MTX), sulfasalazine (SSZ), hydroxychloroquine (HCQ), anti–tumor necrosis factor α monoclonal antibody (infliximab), interleukin‐4 (IL‐4), and IL‐10. Osteoclast formation was assayed by counting cells after staining for tartrate‐resistant acid phosphatase. RANKL expression in RA FLS and RANK expression in PBMCs were assayed by Western blotting, reverse transcription–polymerase chain reaction (RT‐PCR), and real‐time PCR. OPG expression was measured by enzyme‐linked immunosorbent assay, RT‐PCR, and real‐time PCR in cultures of RA FLS.

Results

MTX, SSZ, infliximab, and IL‐4, but not IL‐10 and HCQ, each inhibited osteoclast formation in a dose‐dependent manner. We observed no evidence of synergistic inhibition of osteoclast formation by IL‐4 and IL‐10. High doses of infliximab suppressed the expression of RANK in PBMCs. MTX, SSZ, infliximab, and IL‐4 each inhibited the expression of RANKL in RA FLS in a dose‐dependent manner, and also increased the secretion of OPG in RA FLS supernatants.

Conclusion

MTX, SSZ, infliximab, and IL‐4 inhibit human osteoclastogenesis by modulating the interaction of RANKL, RANK, and OPG. These results are indicative of the underlying mechanisms of the antiresorptive effects of these 4 agents.

📜 SIMILAR VOLUMES

Plasma levels of receptor activator of n
Plasma levels of receptor activator of nuclear factor-κB ligand and osteoprotegerin in patients with neuroblastoma
✍ Donatella Granchi; Alberto Garaventa; Ilaria Amato; Paolo Paolucci; Nicola Baldi 📂 Article 📅 2006 🏛 John Wiley and Sons 🌐 French ⚖ 141 KB

## Abstract Earlier reports showed that the balance between receptor activator of nuclear factor‐κB ligand (RANKL) and its decoy‐receptor osteoprotegerin (OPG) plays an important role in the pathogenesis of metastatic osteolysis induced by neuroblastoma cells. In this study, we investigated whether

In vitro blockade of receptor activator
In vitro blockade of receptor activator of nuclear factor-κB ligand prevents osteoclastogenesis induced by neuroblastoma cells
✍ Donatella Granchi; Ilaria Amato; Luca Battistelli; Sofia Avnet; Sergio Capacciol 📂 Article 📅 2004 🏛 John Wiley and Sons 🌐 French ⚖ 550 KB

## Abstract Proliferation and differentiation of osteoclasts are regulated by a cytokine system that includes RANKL, which binds 2 receptors: RANK, which activates osteoclast differentiation, and osteoprotegerin (OPG), a decoy receptor that limits RANKL action. We investigated the role of the OPG/R

Receptor activator of nuclear factor-κB
Receptor activator of nuclear factor-κB ligand and osteoprotegerin : Potential implications for the pathogenesis and treatment of malignant bone diseases
✍ Lorenz C. Hofbauer; Andreas Neubauer; Armin E. Heufelder 📂 Article 📅 2001 🏛 John Wiley and Sons 🌐 English ⚖ 142 KB 👁 1 views

## Background: The current review summarizes the roles of the ligand, receptor activator of nuclear factor-kappab ligand (rankl), its receptor, receptor activator of nuclear factor-kappab (rank), and its decoy receptor, osteoprotegerin (opg), on osteoclast biology and bone resorption. furthermore,

The antirheumatic drug leflunomide inhib
The antirheumatic drug leflunomide inhibits osteoclastogenesis by interfering with receptor activator of NF-κB ligand–stimulated induction of nuclear factor of activated T cells c1
✍ Makoto Urushibara; Hiroshi Takayanagi; Takako Koga; Sunhwa Kim; Miho Isobe; Yasu 📂 Article 📅 2004 🏛 John Wiley and Sons 🌐 English ⚖ 281 KB 👁 2 views

## Abstract ## Objective Suppression of bone destruction is required as part of an effective therapeutic strategy for autoimmune arthritis. Although numerous antirheumatic drugs are in clinical use, little is known about whether they inhibit bone destruction by acting on activated T cells or other

Simvastatin, 3-hydroxy-3-methylglutaryl
Simvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, suppresses osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand through modulation of NF-κB pathway
✍ Kwang Seok Ahn; Gautam Sethi; Madan M. Chaturvedi; Bharat B. Aggarwal 📂 Article 📅 2008 🏛 John Wiley and Sons 🌐 French ⚖ 631 KB

## Abstract Simvastatin, an inhibitor of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase, is a cholesterol‐lowering drug that may play a role in bone metabolism through a mechanism that is not fully understood. Recently, receptor activator of NF‐κB ligand (RANKL), a member of the TNF superfamily, h