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However, such crosstalk effect in steroid-associated necrosis of femoral head (SANFH) has not been fully explored and evaluated. In this study, early-stage SANFH was induced by two doses of lipopolysaccharide (LPS, 2\u2009mg\/kg\/day) and three doses of methylprednisolone (MPS, 40\u2009mg\/kg\/day). LPS and pyrrolidine dithiocarbamate (PDTC) were administered to activate the TLR4\/NF-\u03baB pathway and selectively block the activation of NF-\u03baB, respectively. Results showed that PDTC treatment significantly reduced\u00a0NF-\u03baB expression, diminished inflammation, and effectively decreased bone resorption processes (osteoclastogenesis, adipogenesis, and apoptosis), which were evidently reinforced after osteonecrosis induction. Moreover, PDTC remarkably increased the interfered Wnt\/\u03b2-catenin pathway and elevated bone formation processes (osteogenesis and angiogenesis). Ultimately, PDTC treatment effectively reduced the incidence of SANFH. Therefore, the excessive activation of TLR4\/NF-\u03baB may interactively suppress the Wnt\/\u03b2-catenin pathway and induce SANFH. Hence, we propose NF-\u03baB-targeted treatment as a novel therapeutic strategy for SANFH.<\/jats:p>","DOI":"10.1038\/s41598-017-12196-8","type":"journal-article","created":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T04:00:43Z","timestamp":1505361643000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Excessive Activation of TLR4\/NF-\u03baB Interactively Suppresses the Canonical Wnt\/\u03b2-catenin Pathway and Induces SANFH in SD Rats"],"prefix":"10.1038","volume":"7","author":[{"given":"Junpeng","family":"Pei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Nan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Dang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunzheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,20]]},"reference":[{"issue":"2","key":"12196_CR1","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.jot.2014.12.002","volume":"3","author":"XH Xie","year":"2015","unstructured":"Xie, X. 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The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. A randomized clinical study. Journal of Bone & Joint Surgery. \n                           87(10), 2155, https:\/\/doi.org\/10.2106\/JBJS.D.02959. (2005).","journal-title":"Journal of Bone & Joint Surgery."},{"issue":"2","key":"12196_CR4","doi-asserted-by":"publisher","first-page":"69","DOI":"10.5435\/JAAOS-D-14-00431","volume":"23","author":"CG Zalavras","year":"2015","unstructured":"Zalavras, C. G. & Lieberman, J. R. Osteonecrosis of the femoral head: evaluation and treatment. J Am Acad Orthop Surg. \n                           23(2), 69\u201370, https:\/\/doi.org\/10.5435\/JAAOS-22-07-455 (2015).","journal-title":"J Am Acad Orthop Surg."},{"issue":"9","key":"12196_CR5","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.1007\/s00167-014-3239-3","volume":"23","author":"VC Fotopoulos","year":"2015","unstructured":"Fotopoulos, V. 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