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Progranulin (PGRN) is known to have anti-inflammatory action by binding to Tumor Necrosis Factor (TNF) receptors and antagonizing TNF\u03b1. Here we report that titanium particles significantly induced PGRN expression in RAW264.7 cells and also in a mouse air-pouch model of inflammation. PGRN-deficiency enhanced, whereas administration of recombinant PGRN effectively inhibited, titanium particle-induced inflammation in an air pouch model. In addition, PGRN also significantly inhibited titanium particle-induced osteoclastogenesis and calvarial osteolysis <jats:italic>in vitro, ex vivo<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Mechanistic studies demonstrated that the inhibition of PGRN on titanium particle induced-inflammation is primarily via neutralizing the titanium particle-activated TNF\u03b1\/NF-\u03baB signaling pathway and this is evidenced by the suppression of particle-induced I\u03baB phosphorylation, NF-\u03baB p65 nuclear translocation and activity of the NF-\u03baB-specific reporter gene. Collectively, these findings not only demonstrate that PGRN plays an important role in inhibiting titanium particle-induced inflammation, but also provide a potential therapeutic agent for the prevention of wear debris-induced inflammation and osteolysis.<\/jats:p>","DOI":"10.1038\/srep20909","type":"journal-article","created":{"date-parts":[[2016,2,11]],"date-time":"2016-02-11T10:58:37Z","timestamp":1455188317000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Progranulin suppresses titanium particle induced inflammatory osteolysis by targeting TNF\u03b1 signaling"],"prefix":"10.1038","volume":"6","author":[{"given":"Yun-peng","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-lu","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing-yun","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander Tianxing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Su","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A.","family":"Einhorn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan-ju","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,2,11]]},"reference":[{"key":"BFsrep20909_CR1","doi-asserted-by":"publisher","first-page":"8937","DOI":"10.1016\/j.biomaterials.2014.06.055","volume":"35","author":"B Tian","year":"2014","unstructured":"Tian, B. et al. 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