S-Space College of Dentistry/School of Dentistry (치과대학/치의학대학원) Dept. of Dentistry (치의학과) Journal Papers (저널논문_치의학과)
Tumor necrosis factor-alpha induces differentiation of human peripheral blood mononuclear cells into osteoclasts through the induction of p21(WAF1/Cip1).
- Kwak, Han Bok; Jin, Hye-Mi; Ha, Hyunil; Kang, Mi-Jin; Lee, Seung Bok; Kim, Hong-Hee; Lee, Zang Hee
- Issue Date
- Biochemical and Biophysical Research Communications 330 (2005) 1080-1086
- Tumor necrosis factor-α (TNF-α) is a multifunctional cytokine that mediates inflammation and induces bone loss caused by excessive bone resorption by osteoclasts. The interaction of TNF-α with its receptor activates several signal transduction pathways, including those of mitogen-activated protein (MAP) kinases (p38, JNK, and ERK) and NF-κB. Signaling from these molecules has been shown to play an important role in osteoclastogenesis. In the present study, we investigated the mechanism of TNF-α-induced osteoclast differentiation in human peripheral blood mononuclear cells (PBMCs). We found that TNF-α alone greatly induced differentiation of PBMCs into osteoclasts. The osteoclast differentiation induced by TNF-α was independent of RANKL binding to its receptor RANK on PBMCs. Furthermore, TNF-α potently activated p38 MAPK, JNK, and NF-κB. Western blotting analysis revealed that p21WAF1/Cip1, a cyclin-dependent kinase (CDK) inhibitor, is significantly induced upon TNF-α stimulation. The induction of p21WAF1/Cip1 during differentiation is responsible for arrest at G0/G1 phase and associated with the JNK pathway. These results suggest that TNF-α regulates osteoclast differentiation through p21WAF1/Cip1 expression and further shows that these events require JNK activity.
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