A Novel Function for Osteoclast Differentiation and Bone Resorption

Overview

Medical University of South Carolina Osteoclasts (OCL) are bone-resorbing cells that differentiate from macrophage precursors in response to receptor activator of nuclear factor kappa-Β (NF-κB) ligand (RANKL). Although NFAT (nuclear factor of activated T-cells) activating protein with ITAM motif 1 (NFAM1) signaling is known to enhance OCL formation and bone resorption activity in Paget’s disease of bone, the regulation of NFAM1 in OCL differentiation and bone resorption remains unclear. Here, I show that the activation of RANKL enhances NFAM1 expression and signaling in vitro in RAW264.7 cells. We first transduced RAW264.7 cells with NFAM1 shRNAmir recombinant lentivirus and stable cells with NFAM1 knockdown (KD) and control wild-type (WT) were established. Condition media obtained from RANKL- stimulated cells showed a significant inhibition of in the levels of cytokines IL-6 (2.5-fold) and TNF-α (2.2-fold) and chemokine ligand 5 (CXCL-5) (3-fold) in NFAM1-KD cells compared to WT. Further, RANKL-stimulation significantly increased p-STAT6 expression (5.5-fold) in WT cells but it was decreased to 2.5-fold in NFAM1-KD cells. In contrast, no changes were detected in STAT3 phosphorylation in these RANKL-stimulated cells. The expression of tartrate- resistant acid phosphatase (TRAP) was remarkably inhibited by NFAM1-KD in pre-OCL cells. Furthermore, the expression of NFATc1, a key transcription factor associated with OCL differentiation, is significantly inhibited in NFAM1-KD cells. Remarkably, lentiviral knockdown of NFAM1 inhibited OCL formation and bone resorption activity in mouse primary bone marrow nonadherent cell cultures. Taken together, these studies identified a novel functional role for NFAM1 in attenuation of osteoclast differentiation and bone resorption.

Awards (1)

• Poster Peer Awardee

Competition history

• JSHS 2020 Category not listed

Resources

• National JSHS abstract book ↗

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