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Nrf2 is a key regulator of osteoclast differentiation and formation, and this study investigated the regulatory mechanism by which Nrf2 promotes osteoclast differentiation after <jats:italic>E. granulosus<\/jats:italic> infection. In vitro, our study revealed that PSC intervention suppressed the expression levels of intracellular Nrf2 and its downstream effector, heme oxygenase-1 (HO-1), while increasing the content of intracellular reactive oxygen species (ROS), thereby promoting osteoclast differentiation. Next, we treated bone marrow mononuclear cells (BMMCs) with protoscoleces (PSC) and found that Nrf2 knockdown significantly promoted osteoclast formation, whereas Nrf2 activation had the opposite effect. We also verified that phosphorylation of the MAPK pathway was promoted after PSC intervention. In vivo, we established an osseous CE model and reported that Nrf2 knockout mice presented more pronounced bone destruction and more active osteoclast differentiation in infected bone tissue. In this study, we demonstrated that Nrf2 plays an important regulatory role in echinococcosis of the bone caused by <jats:italic>E. granulosus<\/jats:italic> infection both in vitro and in vivo. <jats:italic>E. granulosus<\/jats:italic> infection inhibits the expression of Nrf2 in cells, which leads to increased osteoclast differentiation and active bone resorption. This study provides not only a direction for more precise mechanistic research but also a new molecular target for the drug treatment of osseous echinococcosis.<\/jats:p>","DOI":"10.1186\/s13567-025-01510-2","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T09:11:26Z","timestamp":1744449086000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Echinococcus granulosus promotes MAPK pathway-mediated osteoclast differentiation by inhibiting Nrf2 in osseous echinococcosis"],"prefix":"10.1186","volume":"56","author":[{"given":"Yaqing","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhendong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhu","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sibo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenhui","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0120-1699","authenticated-orcid":false,"given":"Haohao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,12]]},"reference":[{"key":"1510_CR1","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1128\/CMR.17.1.107-135.2004","volume":"17","author":"J Eckert","year":"2004","unstructured":"Eckert J, Deplazes P (2004) Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. 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