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Updated: Jun 17, 2026

Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
Published on: January 27, 2023
Fibronectin supports TNF-alpha-induced osteopontin expression through beta1 integrin and ERK in HN-22 cells
Ruchadaporn Kaomongkolgit1, Jeeranan Manokawinchoke, Neeracha Sanchavanakit
1Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Henri-Dunant Road, Pathumwan, Bangkok 10330, Thailand.
Abstract:
The extracellular matrix (ECM), in collaboration with intracellular signal, plays a critical role in the modulation of cellular behavior and function. Herein, we investigated the influence of fibronectin (FN) and tumor necrosis factor-alpha (TNF-alpha) on OPN expression in HN-22, a human head and neck squamous cell carcinoma (HNSCC) cell line. The data showed that TNF-alpha significantly increased OPN expression only in the FN-coated condition. Application of function-blocking antibody directed against beta1 integrin abolished this OPN induction. Moreover, TNF-alpha when added together with activating beta1 integrin antibody is sufficient to induced OPN expression. The combination effect of FN and TNF-alpha was significantly deteriorated by a MEK inhibitor, but not NF-kappaB inhibitor. We further demonstrated that the phosphorylation of ERK1/2 was strongly enhanced by TNF-alpha and FN compared to the application of either one alone. Synergistic effect on ERK1/2 phosphorylation was also detected by TNF-alpha and activating beta1 integrin antibody, whereas inhibitory antibody to beta1 integrin attenuated FN and TNF-alpha-induced phosphorylation of ERK1/2. Our results indicate that FN coordinates TNF-alpha-mediated OPN induction via beta1 integrin-dependent signaling mechanism that activates ERK. The results suggest the critical role of tumor micro-environment signaling networks on the regulation of cytokine expression profiles during tumor progression.
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