1,25-dihydroxyvitamin D3 inhibits the RANKL pathway and impacts on the production of pathway-associated cytokines in early rheumatoid arthritis.

Jing Luo,Xiaofeng Li,Shuangtian Li,Qi Cai,Hongyan Wen,Hui Guo

doi:10.1155/2013/101805

Abstract

Objectives. To study effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on RANKL signaling pathway and pathway-associated cytokines in patients with rheumatoid arthritis (RA). Methods. Receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), IFN-γ, IL-6, TNF-α, IL-17, and IL-4 were examined in 54 patients with incipient RA using a cytometric bead array (CBA) or an enzyme-linked immunosorbent assay (ELISA). Results. After 72 hours of incubation of peripheral blood mononuclear cells (PBMCs) with 1,25(OH)2D3 in RA patients, the levels of RANKL, TNF-α, IL-17 and IL-6 significantly decreased compared to those of the control. 1,25(OH)2D3 had no significantly impact on the levels of OPG, RANKL/OPG, and IL-4. Conclusions. The present study demonstrated that 1,25(OH)2D3 reduced the production of RANKL and the secretion of TNF-α, IL-17, and IL-6 in PBMCs of RA patients, which indicated that 1,25(OH)2D3 might be able to decrease damage of cartilage and bone in RA patients by regulating the expression of RANKL signaling pathway and pathway-associated cytokines.

Highlights

Rheumatoid arthritis (RA) is a common chronic autoimmune disorder characterized by synovial inflammation
We examined the expression of receptor activator of nuclear factor kappa-B ligand (RANKL), OPG, and associated cytokines in the serum of RA patients and healthy control
There was a significant increase in RANKL, IL-17, IL6, and tumor necrosis factor-α (TNF-α) of RA patients when compared with those of healthy control (Table 1)

Summary

Introduction

Rheumatoid arthritis (RA) is a common chronic autoimmune disorder characterized by synovial inflammation. An abnormal proliferation of T lymphocytes is a characteristic of RA. Previous data indicate that the accumulation and proliferation of T lymphocytes occurred prior to bone destruction [4, 5]. T lymphocytes play a role in differentiation and maturation of osteoclasts [6]. T lymphocytes secrete soluble cytokines such as RANKL, macrophage colonystimulating factor (M-CSF), and tumor necrosis factor-α (TNF-α) and thereby directly induce the formation and differentiation of osteoclasts (direct effect) [7,8,9]. T lymphocytes produce interleukins such as IL-1, IL-6, and IL-17, which are absorption-promoting cytokines stimulating the expression of RANKL on the cell surface of mature osteoclasts, mesenchymal cells, or fibroblasts [10,11,12]

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