NFAM1 signaling enhances osteoclast formation and bone resorption activity in Paget's disease of bone

Bone
Yuvaraj SambandamSakamuri V Reddy

Abstract

Paget's disease of bone (PDB) is marked by the focal activity of abnormal osteoclasts (OCLs) with excess bone resorption. We previously detected measles virus nucleocapsid protein (MVNP) transcripts in OCLs from patients with PDB. Also, MVNP stimulates pagetic OCL formation in vitro and in vivo. However, the mechanism by which MVNP induces excess OCLs/bone resorption activity in PDB is unclear. Microarray analysis identified MVNP induction of NFAM1 (NFAT activating protein with ITAM motif 1) expression. Therefore, we hypothesize that MVNP induction of NFAM1 enhances OCL differentiation and bone resorption in PDB. MVNP transduced normal human PBMC showed an increased NFAM1 mRNA expression without RANKL treatment. Further, bone marrow cells from patients with PDB demonstrated elevated levels of NFAM1 mRNA expression. Interestingly, shRNA suppression of NFAM1 inhibits MVNP induced OCL differentiation and bone resorption activity in mouse bone marrow cultures. Live cell widefield fluorescence microscopy analysis revealed that MVNP induced intracellular Ca2+oscillations and levels were significantly reduced in NFAM1 suppressed preosteoclasts. Further, western blot analysis demonstrates that shRNA against NFAM1 inhibits MVNP stimulat...Continue Reading

Citations

Jan 13, 2018·Journal of Cellular Physiology·Yuvaraj SambandamSakamuri V Reddy
Sep 26, 2019·Seminars in Immunopathology·Asuka Terashima, Hiroshi Takayanagi
Jul 7, 2021·Journal of Cellular Biochemistry·Purushoth EthirajSakamuri V Reddy

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