The Inactivation of ERK1/2, p38 and NF-kappa B Is Involved in the Down-Regulation of Osteoclastogenesis and Function by A2B Adenosine Receptor Stimulation
- Authors
- Kim, Bo Hyun; Oh, Ju Hee; Lee, Na Kyung
- Issue Date
- Oct-2017
- Publisher
- 한국분자세포생물학회
- Keywords
- A2B adenosine receptor; osteoclastogenesis; RANKL
- Citation
- Molecules and Cells, v.40, no.10, pp 752 - 760
- Pages
- 9
- Journal Title
- Molecules and Cells
- Volume
- 40
- Number
- 10
- Start Page
- 752
- End Page
- 760
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/7147
- DOI
- 10.14348/molcells.2017.0098
- ISSN
- 1016-8478
0219-1032
- Abstract
- A2B adenosine receptor (A2BAR) is known to be the regulator of bone homeostasis, but its regulatory mechanisms in osteoclast formation are less well-defined. Here, we demonstrate the effect of A2BAR stimulation on osteoclast differentiation and activity by RANKL. A2BAR was expressed in bone marrow-derived monocyte/macrophage (BMM) and RANKL increased A2BAR expression during osteoclastogenesis. A2BAR stimulation with its specific agonist BAY 60-6583 was sufficient to inhibit the activation of ERK1/2, p38 MAP kinases and NF-kappa B by RANKL as well as it abrogated cell-cell fusion in the late stage of osteoclast differentiation. Stimulation of A2BAR suppressed the expression of osteoclast marker genes, such as c-Fos, TRAP, Cathepsin-K and NFATc1, induced by RANKL, and transcriptional activity of NFATc1 was also inhibited by stimulation of A2BAR. A2BAR stimulation caused a notable reduction in the expression of Atp6v0d2 and DC-STAMP related to cell-cell fusion of osteoclasts. Especially, a decrease in bone resorption activity through suppression of actin ring formation by A2BAR stimulation was observed. Taken together, these results suggest that A2BAR stimulation inhibits the activation of ERK1/2, p38 and NF-kappa B by RANKL, which suppresses the induction of osteoclast marker genes, thus contributing to the decrease in osteoclast cell-cell fusion and bone resorption activity.
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Collections - College of Medical Sciences > Department of Biomedical Laboratory Science > 1. Journal Articles
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