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Elucidating the mechanism underlying osteoclast differentiation is important to improve our understanding of the pathophysiologies related to skeletal diseases and osteolytic metastasis in cancer. Sex-determining region Y-box containing gene 2 (SOX2), a stemness marker, is known to affect osteoblast differentiation and cancer metastasis. However, its role in osteoclastogenesis has not been investigated to date. Here, we report that SOX2 protein and mRNA expression was upregulated during osteoclast differentiation. The overexpression or knockdown of SOX2 in osteoclast precursor cells enhanced or suppressed, respectively, receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation and migration, and nuclear factor of activated T-cell c1 (NFATc1) and factor-associated suicide ligand (FASL) expression. In addition, epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK) activation were regulated by SOX2 expression; both EGFR and ERK inhibitors abrogated the SOX2 overexpression-induced increase in osteoclast differentiation and NFATc1 expression under RANKL stimulation. Overall, these results suggest SOX2 as a positive regulatory factor during osteoclast differentiation partly through the EGFR and ERK signaling pathways, highlighting a new potential target for restoring abnormal osteoclast activation.
This article was published in the following journal.
Name: Biochemical and biophysical research communications
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A growth differentiation factor that plays a regulatory role as a paracrine factor for a diverse array of cell types during EMBRYONIC DEVELOPMENT and in the adult tissues. Growth differentiation factor 2 is also a potent regulator of CHONDROGENESIS and was previously referred to as bone morphogenetic protein 9.
A humanized monoclonal antibody and an inhibitor of the RANK LIGAND, which regulates OSTEOCLAST differentiation and bone remodeling. It is used as a BONE DENSITY CONSERVATION AGENT in the treatment of OSTEOPOROSIS.
A DNA binding protein, transcriptional regulator, and proto-oncogene protein that contains 10 CYS2-HIS2 ZINC FINGERS. It functions as a positive or negative regulator of expression for target genes involved in organism development.
A basic helix-loop-helix transcription factor that plays a critical role in HEMATOPOIESIS and as a positive regulator in the differentiation of ERYTHROID CELLS. Chromosome translocations involving the TAL-1 gene are associated with T-CELL ACUTE LYMPHOCYTIC LEUKEMIA.
A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.
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