Tusc2/Fus1 regulates osteoclast differentiation through NF-κB and NFATc1
نویسندگان
چکیده
Tumor suppressor candidate 2 (Tusc2, also known as Fus1) regulates calcium signaling, and Ca2+-dependent nuclear factor of activated T-cells (NFAT) and nuclear factor kappa B (NF-κB) pathways, which play roles in osteoclast differentiation. However, the role of Tusc2 in osteoclasts remains unknown. Here, we report that Tusc2 positively regulates the differentiation of osteoclasts. Overexpression of Tusc2 in osteoclast precursor cells enhanced receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation. In contrast, small interfering RNA-mediated knockdown of Tusc2 strongly inhibited osteoclast differentiation. In addition, Tusc2 induced the activation of RANKL-mediated NF-κB and calcium/calmodulin-dependent kinase IV (CaMKIV)/cAMP-response element (CRE)-binding protein CREB signaling cascades. Taken together, these results suggest that Tusc2 acts as a positive regulator of RANKL-mediated osteoclast differentiation. [BMB Reports 2017; 50(9): 454-459].
منابع مشابه
Pim-1 regulates RANKL-induced osteoclastogenesis via NF-κB activation and NFATc1 induction.
Pim kinases are emerging as important mediators of cytokine signaling pathways in hematopoietic cells. In this study, we demonstrate that Pim-1 positively regulates RANKL-induced osteoclastogenesis and that Pim-1 expression can be upregulated by RANKL signaling during osteoclast differentiation. The silencing of Pim-1 by RNA interference or overexpression of a dominant negative form of Pim-1 (P...
متن کاملTLR2-dependent modulation of osteoclastogenesis by Porphyromonas gingivalis through differential induction of NFATc1 and NF-kappaB.
Osteolytic diseases, including rheumatoid arthritis, osteomyelitis, and periodontitis, are usually associated with bacterial infections. However, the precise mechanisms by which bacteria induce bone loss still remain unclear. Evidence exists that Toll-like receptor (TLR) signaling regulates both inflammation and bone metabolism and that the receptor activator of NF-κB ligand (RANKL) and its rec...
متن کاملErratum to: Sophorae Flos extract inhibits RANKL-induced osteoclast differentiation by suppressing the NF-κB/NFATc1 pathway in mouse bone marrow cells
BACKGROUND Sophorae Flos (SF) is a composite of flowers and buds of Styphnolobium japonicum (L.) Schott and has been used in traditional Korean and Chinese medicine for the treatment of hemostasis and inflammation. Previous studies reported that SF possesses anti-obesity properties, as well as anti-allergic, anti-proliferative, and anti-inflammatory activities. However, the effect of SF in bone...
متن کاملRegulation of NFATc1 in Osteoclast Differentiation
Osteoclasts are unique cells that degrade the bone matrix. These large multinucleated cells differentiate from the monocyte/macrophage lineage upon stimulation by two essential cytokines, macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL). Activation of transcription factors such as microphthalmia transcription factor (MITF), c-F...
متن کاملEarly growth response gene2 negatively modulates osteoclast differentiation by up-regulating Id helix-loop-helix proteins
INTRODUCTION Osteoclasts are derived from hematopoietic precursors in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). Binding of RANKL to its receptor RANK activates NF-κB, c-fos, and NFATc1, all of which are essential for osteoclastogenesis. The inhibitor of differentiation/DNA binding (Id), helix-loop-helix (HLH) proteins act as dom...
متن کامل