2. Academic Validation
  3. Pinosylvin Inhibits Inflammatory and Osteoclastogenesis via NLRP3 Inflammasome

Pinosylvin Inhibits Inflammatory and Osteoclastogenesis via NLRP3 Inflammasome

  • Adv Sci (Weinh). 2025 Jun 10:e01532. doi: 10.1002/advs.202501532.
Wei Zhang 1,  Xiangbing Wu 2,  Wenming Li 1,  Haifeng Zhang 3,  Yijun Wang 1,  Jing Xu 4,  Wenhao Li 1,  Yi Qin 1,  Zebin Wu 1,  Gaoran Ge 1,  Shujun Lv 5,  Lu Mao 6,  Liangliang Wang 7,  Dechun Geng 1
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, China.
  • 2 Department of Implant Dentistry, Suzhou Stomatological Hospital, Suzhou, Jiangsu, 215005, China.
  • 3 Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.85 Wujin Road, Hongkou District, Shanghai, 200080, China.
  • 4 Department of Anesthesiology, Affiliated Hospital of Jiangsu University, 438 Jie Fang Road, Zhenjiang, Jiangsu, 212001, China.
  • 5 Department of Orthopedics, Hai'an People's Hospital, Hai'an, Jiangsu, 226000, China.
  • 6 Department of Spine Surgery, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, 210009, China.
  • 7 Department of Orthopedics, the Second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213000, China.
PMID: 40492417 DOI: 10.1002/advs.202501532
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.

Keywords

NEK7; Pinosylvin; inflammatory related bone loss; osteoclastogenesis; pyroptosis.

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