The Specific Role of Vesicle-Associated Membrane Protein-Associated Protein B/C(VapB) As a Regulator of Osteoclastogenesis Via Modulation of Phospholipase Cã(PLCã2-Ca2+-NFAT Signaling

Chang-Hoon Lee¹, Wan-Hee Yoo², Jin-Jung Choi³, Myong-Joo Hong⁴, Ji-Min Kim⁵ and Sik-Won Choi⁶, ¹Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Chonbuk, South Korea, ²Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Jeonju, South Korea, ³Internal Medicine, CHA University Hospital, Seongnam, South Korea, ⁴Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Jeonju, South Korea, ⁵Division of Rheumatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea, ⁶Department of Anatomy and Institute for Skeletal Disease, School of medicine, Wonkwang university, Iksan, Chonbuk, South Korea

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: osteoclasts and phospholipase, RANK/RANKL pathway

Session Information

Title: Osteoporosis and Metabolic Bone Disease

Session Type: Abstract Submissions (ACR)

Background/Purpose: Recently, Vesicle-Associated Membrane Protein-Associated Protein B/C(VapB) has been shown to regulate calcium homeostasis in myotrophic lateral sclerosis. Calcium signalingis also important in metabolic bone diseases, but the role of VapB in the generation of osteoclasts for bone resorption during osteoclastogenesis is not known. Therefore, we investigated the role of VapB in RANKL-induced osteoclast differentiation

Methods: Osteoclast formation was evaluated in bone marrow cells (BMC) in specific condition with over-expression of VapB or down- regulation of VapB during receptor activator of NF-κB ligand (RANKL)- mediated osteoclastogenesis.. The expression of c-fos and NFATc1 mRNA in osteoclast precursor were assessed by RT-PCR. The levels of c-fos and NFATc1 protein were assessed by western blot. Also the mitogen-activated protein (MAPK)s pathways were measured using Western blot analysis.

Results: We found that VapB is induced during osteoclastogenesis, and regulates osteoclast differentiation by modulating NFATc1. The results suggest that VapB regulates osteoclastogenesis via of Phospholipase Cγ (PLCγ)2-Ca2+-NFAT signaling. The involvement of PLCγ2-Ca2+-NFAT signaling in VapB-regulated osteoclastogenesis was confirmed by a pharmacological study.

Conclusion: Taken together, these results indicate that VapB positively regulates RANKL-mediated osteoclastogenesis via PLCγ2-Ca2+-NFAT signaling and may provide a basis for exploring the therapeutic potential of VapB silencing for metabolic bone diseases, such as osteoporosis and rheumatoid arthritis

Disclosure:

C. H. Lee,
None;

W. H. Yoo,
None;

J. J. Choi,
None;

M. J. Hong,
None;

J. M. Kim,
None;

S. W. Choi,
None.

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