2. Academic Validation
  3. Ethyl caffeate inhibits macrophage polarization via SIRT1/NF-κB to attenuate traumatic heterotopic ossification in mice

Ethyl caffeate inhibits macrophage polarization via SIRT1/NF-κB to attenuate traumatic heterotopic ossification in mice

  • Biomed Pharmacother. 2023 May:161:114508. doi: 10.1016/j.biopha.2023.114508.
Hui Wang 1,  Dezhi Song 1,  Linhua Wei 2,  Linke Huang 3,  Donglei Wei 1,  Yuangang Su 1,  Jiamin Liang 1,  Haoyu Lian 1,  Jinmin Zhao 4,  Qian Liu 5
Affiliations

Affiliations

  • 1 Research Centre for Regenerative Medicine, Orthopaedic Department, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning 530021, China.
  • 2 Research Centre for Regenerative Medicine, Orthopaedic Department, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning 530021, China; The Affiliated Nanning Infectious Disease Hospital of Guangxi Medical University, the Fourth People's Hospital of Nanning, Nanning 530000, China.
  • 3 Department of Orthopaedics, the Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China.
  • 4 Research Centre for Regenerative Medicine, Orthopaedic Department, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning 530021, China. Electronic address: [email protected].
  • 5 Research Centre for Regenerative Medicine, Orthopaedic Department, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China. Electronic address: [email protected].
PMID: 37002582 DOI: 10.1016/j.biopha.2023.114508
Abstract

Heterotopic ossification (HO) denotes the presence of mature bone tissue in soft tissues or around joints. Inflammation is a key driver of traumatic HO, and macrophages play an important role in this process. Ethyl caffeate (ECF), a critical active compound found in Petunia, exerts significant anti-inflammatory effects. Herein, we established a mouse model of HO by transection of the Achilles tendon and back burn and found abundant macrophage infiltration in the early stage of HO, which decreased with time. In vitro and in vivo experiments indicated that ECF inhibited macrophage polarization, and mechanistic studies showed that it inhibited the SIRT1/NF-κB signalling pathway, thereby suppressing the release of downstream inflammatory cytokines. ECF reduced HO in mice, and its effect was comparable to indomethacin (INDO). In vitro studies revealed that ECF did not directly affect the mineralization of mesenchymal stem cells (MSCs) or osteogenic differentiation but inhibited these processes by reducing the level of inflammatory cytokines in the conditioned medium (CM). Thus, M1 macrophages may play a crucial role in the pathogenesis of HO, and ECF is a prospective candidate for the prevention of trauma-induced HO. DATA AVAILABILITY: Data will be made available on request.

Keywords

Ethyl caffeate; Heterotopic ossification; Macrophage polarization; SIRT1.

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