{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang W"],"funding":["Foundation of National Center for Translational Medicine","Jiangsu Medical Research Project","Suzhou Applied Basic Research (Medical and Health) General Project","Program of Suzhou Health Commission","Postgraduate Research & Practice Innovation Program of Jiangsu Province","Priority Academic Program Development of Jiangsu Higher Education Institutions","Changzhou Sci&Tech Program","National Natural Science Foundation of China","National and Local Engineering Laboratory of New Functional Polymer Materials","Top Talent of Changzhou\"The14th Five-Year Plan\"High-Level Health Talents Training Project","Project of MOE Key Laboratory of Geriatric Diseases and Immunology"],"pagination":["e01532"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12376636"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(31)"],"pubmed_abstract":["Pro-inflammatory cytokines such as TNF, IL-1, and IL-6 trigger aberrant osteoclastogenesis and result in massive bone loss. During RANKL-induced osteoclastogenesis, pyroptosis of macrophages/preosteoclasts acts as a pivotal mechanism for IL-1β release, thereby promoting osteoclast maturation and bone resorption. In the current study, it is observed that Pinosylvin (PIN), a compound extracted from European red pine, selectively inhibits LPS- and RANKL-induced release of IL-1β effectively reducing osteoclastogenesis. Notably, PIN inhibits the assembly of NLRP3 and the cleavage of GSDMD, pro-IL-1β, and pro-caspase-1, suggesting its therapeutic effects are NLRP3-targeted. Mechanistically, PIN blockes the NEK7/NLRP3 interaction, but not the NLRP3/ASC interaction, through its 3,5-dihydroxy groups by binding to NEK7, thereby inhibiting subsequent pyroptosis and osteoclastogenesis. Importantly, PIN alleviates inflammatory bone loss due to estrogen deficiency, reduces cranial bone destruction from local LPS injections, and improves survival in LPS-induced septic mice. This study uncovers the specific mechanism behind PIN's potent anti-inflammatory effects and identifies a new therapeutic target for NLRP3-driven diseases."],"journal":["Advanced science (Weinheim, Baden-Wurttemberg, Germany)"],"pubmed_title":["Pinosylvin Inhibits Inflammatory and Osteoclastogenesis via NLRP3 Inflammasome."],"pmcid":["PMC12376636"],"funding_grant_id":["82472525","SYW2024061","GSWS2022002","KYCX22_3217","CJ20230069","82272567","KJS2502","SDGC2205","ZD2022014","SUITM-202403","2022CZBJ060"],"pubmed_authors":["Ge G","Zhang H","Qin Y","Mao L","Xu J","Wang L","Zhang W","Li W","Wu Z","Geng D","Lv S","Wang Y","Wu X"],"additional_accession":[]},"is_claimable":false,"name":"Pinosylvin Inhibits Inflammatory and Osteoclastogenesis via NLRP3 Inflammasome.","description":"Pro-inflammatory cytokines such as TNF, IL-1, and IL-6 trigger aberrant osteoclastogenesis and result in massive bone loss. During RANKL-induced osteoclastogenesis, pyroptosis of macrophages/preosteoclasts acts as a pivotal mechanism for IL-1β release, thereby promoting osteoclast maturation and bone resorption. In the current study, it is observed that Pinosylvin (PIN), a compound extracted from European red pine, selectively inhibits LPS- and RANKL-induced release of IL-1β effectively reducing osteoclastogenesis. Notably, PIN inhibits the assembly of NLRP3 and the cleavage of GSDMD, pro-IL-1β, and pro-caspase-1, suggesting its therapeutic effects are NLRP3-targeted. Mechanistically, PIN blockes the NEK7/NLRP3 interaction, but not the NLRP3/ASC interaction, through its 3,5-dihydroxy groups by binding to NEK7, thereby inhibiting subsequent pyroptosis and osteoclastogenesis. Importantly, PIN alleviates inflammatory bone loss due to estrogen deficiency, reduces cranial bone destruction from local LPS injections, and improves survival in LPS-induced septic mice. This study uncovers the specific mechanism behind PIN's potent anti-inflammatory effects and identifies a new therapeutic target for NLRP3-driven diseases.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-09T17:49:21.979Z","creation":"2026-04-08T01:08:29.854Z"},"accession":"S-EPMC12376636","cross_references":{"pubmed":["40492417"],"doi":["10.1002/advs.202501532"]}}