Session 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
C. H. Lee,
W. H. Yoo,
J. J. Choi,
M. J. Hong,
J. M. Kim,
S. W. Choi,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-specific-role-of-vesicle-associated-membrane-protein-associated-protein-bcvapb-as-a-regulator-of-osteoclastogenesis-via-modulation-of-phospholipase-caplca2-ca2-nfat-signaling/