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Low concentrations of carbon monoxide (CO) are known to decrease inflammation and OC-mediated bone erosion but the molecular mechanism is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Low-concentrations of CO (250\u00a0ppm) 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.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1752-0509-8-57","type":"journal-article","created":{"date-parts":[[2014,5,18]],"date-time":"2014-05-18T01:02:15Z","timestamp":1400374935000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Interactomics profiling of the negative regulatory function of carbon monoxide on RANKL-treated RAW 264.7 cells during osteoclastogenesis"],"prefix":"10.1186","volume":"8","author":[{"given":"Feng-Jen","family":"Tseng","sequence":"first","affiliation":[]},{"given":"Wei-Tso","family":"Chia","sequence":"additional","affiliation":[]},{"given":"Jia-Fwu","family":"Shyu","sequence":"additional","affiliation":[]},{"given":"Guo-Hau","family":"Gou","sequence":"additional","affiliation":[]},{"given":"Huey-Kang","family":"Sytwu","sequence":"additional","affiliation":[]},{"given":"Ching-Wu","family":"Hsia","sequence":"additional","affiliation":[]},{"given":"Min-Jen","family":"Tseng","sequence":"additional","affiliation":[]},{"given":"Ru-Yu","family":"Pan","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2014,5,18]]},"reference":[{"key":"1328_CR1","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/0002-9343(71)90113-6","volume":"50","author":"H Rasmussen","year":"1971","unstructured":"Rasmussen H: Ionic and hormonal control of calcium homeostasis. 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