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TNF-α, one of the most potent pro-inflammatory cytokines, plays a critical role in inhibition of osteoblast differentiation and bone regeneration in persistent inflammatory microenvironment. To explore the mechanism, quantitative proteomics based on iTRAQ and MRM was employed. The results showed 6 proteins involved in BMP-2 induced osteoblast differentiation inhibition by TNF-α: Periostin, Protein S100-A4, ATPase inhibitor, Cytochrome b5, SERCA3, and ELP2. The altered proteins were involved in molecular transport, tissue development, energy metabolism, and inflammation. One specific protein, ELP2 (STAT3-interacting protein 1, StIP1) up-regulated in the inhibition of osteoblast differentiation by TNF-α was verified to play a critical role in STAT3 pathway. Overexpression or knockdown of ELP2 in C2C12 and MC3T3-E1 cells affected osteoblast differentiation inhibition induced by TNF-α. These results highlight the function of ELP2 in inflammatory microenvironment, ELP2 up-regulation and STAT3 pathway activation may down-regulate BMPR2, then BMP-2 was blocked and osteoblast differentiation inhibited. The protein-expression profile revealed here should offer at least partly new clues to understand the mechanism of osteoblast differentiation inhibition by inflammation.
Pubmed ID: 25486498
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Database that represents a centralized platform to visually depict and integrate information pertaining to domain architecture, post-translational modifications, interaction networks and disease association for each protein in the human proteome. All the information in HPRD has been manually extracted from the literature by expert biologists who read, interpret and analyze the published data.
View all literature mentionsSoftware tool as Windows client application for targeted proteomics method creation and quantitative data analysis. Open source document editor for creating and analyzing targeted proteomics experiments. Used for large scale quantitative mass spectrometry studies in life sciences.
View all literature mentionsSoftware tool for protein identification and relative protein expression analysis. Used in protein research to identify proteins and search large numbers of post translational modifications. Compatible with all proteomics MS/MS systems.
View all literature mentions