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Our previous study showed necroptosis accelerated the loss of osteocytes in E2 deficiency-induced osteoporosis in rats in addition to apoptosis, but the mechanism involved remains. Necroptosis is a caspase-independent form of programmed cell death. In the necroptosis pathway, receptor interaction proteins 1 and 3 (RIP1\/3) play vital roles. Necrostatin-1 (Nec-1) has been confirmed to be a specific inhibitor of necroptosis. However, the effect of Nec-1 on postmenopausal osteoporosis remains ambiguous. The aim of this study was to investigate the effect of Nec-1 on osteocytes in ovariectomized (OVX) rats. We found that an increased number of necroptotic osteocytes was related to the production of tumor necrosis factor-alpha (TNF-\u03b1) in OVX rats. Treatment with Nec-1 significantly decreased RIP1 and RIP3 expression in OVX rats and inhibited osteocyte necroptosis induced by TNF-\u03b1 <jats:italic>in vitro<\/jats:italic>. Both E2 and Nec-1 treatment markedly ameliorated trabecular bone deterioration. Nec-1 also significantly elevated the levels of bone formation markers and decreased bone resorption markers. These data suggest that the role of Nec-1 on alleviating bone loss might be associated with Nec-1 restraining TNF-\u03b1-induced osteocyte necroptosis in rats with E2 deficiency-induced osteoporosis. This process may represent a novel therapeutic strategy for the treatment of postmenopausal osteoporosis.<\/jats:p>","DOI":"10.1038\/srep33803","type":"journal-article","created":{"date-parts":[[2016,10,5]],"date-time":"2016-10-05T09:43:58Z","timestamp":1475660638000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Necrostatin-1 treatment inhibits osteocyte necroptosis and trabecular deterioration in ovariectomized rats"],"prefix":"10.1038","volume":"6","author":[{"given":"Hongwang","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weikang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianming","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,5]]},"reference":[{"key":"BFsrep33803_CR1","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1111\/j.1749-6632.2010.05813.x","volume":"1211","author":"FA Syed","year":"2010","unstructured":"Syed, F. 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