{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:58:19Z","timestamp":1789041499640,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Clonorchis sinensis<\/jats:italic>\n                      crude antigen (\n                      <jats:italic>Cs<\/jats:italic>\n                      CA) is recognized for its immunomodulatory capacity in host\u2010pathogen interactions and immune\u2010related pathologies, its direct impact on bone remodeling cells remains underexplored. Although prior studies demonstrate\n                      <jats:italic>Cs<\/jats:italic>\n                      CA\u2010mediated suppression of inflammatory bone formation in ankylosing spondylitis, the specific regulatory effects on osteoclastogenesis and associated molecular mechanisms remain elusive. This study aimed to investigate the impact of\n                      <jats:italic>Cs<\/jats:italic>\n                      CA on osteoclast differentiation and its potential molecular mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The cytotoxicity of\n                      <jats:italic>Cs<\/jats:italic>\n                      CA on mouse bone marrow\u2013derived macrophages (BMMs) was evaluated using the CCK\u20108 assay. At the established non\u2010cytotoxic dose, the effects of\n                      <jats:italic>Cs<\/jats:italic>\n                      CA on osteoclast morphology and activity were observed via TRAcP staining and F\u2010actin ring formation assay. Expression of osteoclast differentiation\u2010related genes and proteins was analyzed by combined RT\u2010qPCR and Western Blot. RNA\u2010seq was performed to identify\n                      <jats:italic>Cs<\/jats:italic>\n                      CA\u2010regulated signaling pathways during osteoclast differentiation, followed by validation of key pathway components through Western Blot and immunofluorescence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Cs<\/jats:italic>\n                      CA exhibited no significant cytotoxicity on BMMs at concentrations \u2264\u200940\u2009\u03bcg\/mL. TRAcP staining revealed a significant reduction in osteoclast numbers in\n                      <jats:italic>Cs<\/jats:italic>\n                      CA\u2010treated groups. F\u2010actin ring formation assays demonstrated abnormal cytoskeletal structures. RT\u2010PCR results showed significantly downregulated expression of osteoclast differentiation\u2010related genes, including\n                      <jats:italic>NFATc1<\/jats:italic>\n                      ,\n                      <jats:italic>c\u2010Fos<\/jats:italic>\n                      ,\n                      <jats:italic>Acp5<\/jats:italic>\n                      ,\n                      <jats:italic>CTSK<\/jats:italic>\n                      and\n                      <jats:italic>MMP\u20109<\/jats:italic>\n                      . Western Blot confirmed reduced protein expression levels of NFATc1 and c\u2010Fos. RNA\u2010seq analysis combined with experimental validation by Western Blot and immunofluorescence confirmed that\n                      <jats:italic>Cs<\/jats:italic>\n                      CA primarily inhibits osteoclast differentiation through the NF\u2010\u03baB and MAPK signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Cs<\/jats:italic>\n                      CA inhibits the formation and function of osteoclasts by suppressing the expression of key genes involved in osteoclast differentiation through the inhibition of the NF\u2010\u03baB and MAPK signaling pathways. This study elucidates the mechanism by which\n                      <jats:italic>Cs<\/jats:italic>\n                      CA regulates osteoclasts and suggests its translational potential in preventing and treating hyper\u2010resorptive bone diseases such as osteoporosis and bone metastasis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70292","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T07:06:44Z","timestamp":1762412804000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>Clonorchis sinensis<\/i>\n                    Crude Antigen Suppresses Osteoclast Differentiation via Modulation of the NF\u2010\u03baB and MAPK Signaling Pathway"],"prefix":"10.1002","volume":"13","author":[{"given":"Lili","family":"Tang","sequence":"first","affiliation":[{"name":"Parasitology Department, School of Basic Medical Sciences Guangxi Medical 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