ELP2 negatively regulates osteoblastic differentiation impaired by tumor necrosis factor α in MC3T3-E1 cells through STAT3 activation.
Tumor necrosis factor-α (TNF-α) is a pluripotent signaling molecule. The biological effect of TNF-α includes slowing down osteogenic differentiation, which can lead to bone dysplasia in long-term inflammatory microenvironments. Signal transducer and activator of transcription 3 (STAT3)-interacting protein 1 (StIP1, also known as elongator complex protein 2, ELP2) play a role in inhibiting TNF-α-induced osteoblast differentiation. In the present study, we investigated whether and how ELP2 activation mediates the effects of TNF-α on osteoblastic differentiation. Using in vitro cell cultures of preosteoblastic MC3T3-E1 cells, we found that TNF-α inhibited osteoblastic differentiation accompanied by an increase in ELP2 expression and STAT3 activation. Forced ELP2 expression inhibited osteogenic differentiation of MC3T3-E1 cells, with a decrease in the expression of osteoblast marker genes, alkaline phosphatase activity, and matrix mineralization capacity. In contrast, ELP2 silencing ameliorated osteogenic differentiation in MC3T3-E1 cells, even after TNF-α stimulation. The TNF-α-induced inhibitory effect on osteoblastic differentiation was therefore mediated by ELP2, which was associated with Janus kinase 2 (JAK2)/STAT3 activation. These results suggest that ELP2 is upregulated at the differentiation of MC3T3-E1 cells into osteoblasts and inhibits osteogenic differentiation in response to TNF-α through STAT3 activation.
['Xu|Chang-Peng|CP|0000-0001-6349-0842', 'Sun|Hong-Tao|HT|', 'Yang|Ya-Jun|YJ|', 'Cui|Zhuang|Z|', 'Wang|Jian|J|', 'Yu|Bin|B|', 'Wang|Fa-Zheng|FZ|', 'Yang|Qing-Po|QP|', 'Qi|Yong|Y|']
D016475:3T3 Cells D000818:Animals D002454:Cell Differentiation D047908:Intracellular Signaling Peptides and Proteins D053614:Janus Kinase 2 D051379:Mice D010006:Osteoblasts D010012:Osteogenesis D050796:STAT3 Transcription Factor D015398:Signal Transduction D014409:Tumor Necrosis Factor-alpha
ELP2 osteoblastic differentiation tumor necrosis factor-α signal transducer and activator of transcription 3