Interactomics profiling of the negative regulatory function of carbon monoxide on RANKL-treated RAW 264.7 cells during osteoclastogenesis

BMC Systems Biology

Ru-Yu Pan³  Min-Jen Tseng⁴  Ching-Wu Hsia⁴  Huey-Kang Sytwu⁵  Guo-Hau Gou³  Jia-Fwu Shyu¹  Wei-Tso Chia⁶  Feng-Jen Tseng² 

[1] Department of Biology and Anatomy, National Defense Medical Center, Neihu 114, Taipei, Taiwan, Republic of China;Department of Orthopedics, Hualien Armed Force Hospital, Hualien 971, Taiwan, Republic of China;Department of Orthopaedics, Tri-Service General Hospital, National Defense Medical Center, Neihu 114, Taipei, Taiwan, Republic of China;Department of Life Science, National Chung Cheng University, 168 University Road, Minhsiung, Chiayi 621, Republic of China;Graduate Institute of Medical Science, National Defense Medical Center, Neihu 114, Taipei, Taiwan, Republic of China;Department of Health, Hsin Chu General Hospital, Hsinchu 300, Taiwan, Republic of China

关键词: RAW 264.7;    RANKL;    Interactome;    Osteoclastogenesis;    Carbon monoxide;   

Others  :  866374
DOI  :  10.1186/1752-0509-8-57

 received in 2012-12-27, accepted in 2014-05-12,  发布年份 2014

【 摘 要 】

Background

During osteoclastogenesis, the maturation of osteoclast (OC) progenitors is stimulated by the receptor activator of nuclear factor-κB ligand (RANKL). Excess OC production plays a critical role in the pathogenesis of inflammatory bone disorders. Conversely, the inhibition of abnormal OC proliferation reduces inflammation-induced bone loss. Low concentrations of carbon monoxide (CO) are known to decrease inflammation and OC-mediated bone erosion but the molecular mechanism is unknown.

Results

To obtain insight into the biological function of CO, cultured RANKL-treated RAW 264.7 cells were used in an in vitro experimental model of osteoclastogenesis. The results showed that CO inhibited: 1) tartrate-resistant acid phosphatase (TRAP)-positive cell formation; 2) F-actin ring production; 3) c-fos pathway activation; 4) the expression of cathepsin K, TRAP, calcitonin receptor, and matrix metalloproteinase-9 mRNAs; 5) the expression of nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 in translation. Protein-protein interaction analysis predicted mitogen-activated protein kinase kinase kinase 4 as the controlling hub.

Conclusions

Low-concentrations of CO (250 ppm) may inhibit osteoclastogenesis. Data from STRING- and IPA-based interactome analyses suggested that the expression of proteins with the functions of signal transduction, enzymes, and epigenetic regulation are significantly altered by CO during RANKL-induced osteoclastogenesis. Our study provides the first interactome analysis of osteoclastogenesis, the results of which supported the negative regulation of OC differentiation by CO.

【 授权许可】

   
2014 Tseng et al.; licensee BioMed Central Ltd.

【 图 表 】

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