Pinosylvin Inhibits Inflammatory and Osteoclastogenesis via NLRP3 Inflammasome
Source abstract
Abstract
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.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Inflammasome and immune disorders · Spondyloarthritis Studies and Treatments · Osteomyelitis and Bone Disorders Research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Orthopaedics The First Affiliated Hospital of Soochow University No. 188 Shizi Street Suzhou Jiangsu 215006 China
Department of Implant Dentistry Suzhou Stomatological Hospital Suzhou Jiangsu 215005 China
Department of Orthopaedics Shanghai General Hospital Shanghai Jiao Tong University School of Medicine No.85 Wujin Road, Hongkou District Shanghai 200080 China
Department of Anesthesiology Affiliated Hospital of Jiangsu University 438 Jie Fang Road Zhenjiang Jiangsu 212001 China
Department of Orthopedics Hai'an People's Hospital Hai'an Jiangsu 226000 China
Department of Spine Surgery Zhongda Hospital Southeast University Nanjing Jiangsu 210009 China
Department of Orthopedics the Second People's Hospital of Changzhou the Third Affiliated Hospital of Nanjing Medical University Changzhou Jiangsu 213000 China
Funding
National Natural Science Foundation of China · Priority Academic Program Development of Jiangsu Higher Education Institutions
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