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<p>Temporomandibular joint osteoarthritis (TMJOA) involves progressive synovial inflammation-driven cartilage degeneration. While thermotherapy empirically alleviates symptoms, its immunomodulatory mechanism remains elucidated. Here, we revealed that targeted mild hyperthermia reprogramed synovial M1 macrophages via NF-κB pathway suppression, shifting their secretome to attenuate chondrocyte catabolism while enhancing anabolism. This thermally-modified macrophage conditioned medium concurrently promoted osteogenic mineralization. Capitalizing on this, we engineered folic acid-conjugated Y8 nanocomposites (FA-Y8 NPs) for precision M1-targeting photothermal therapy. Under 808&#xa0;nm irradiation, FA-Y8 NPs achieved localized photothermal reprogramming of synovial M1 macrophages and attenuating cartilage degradation in CFA-induced TMJOA mice. This study reveals thermal immunomodulation of synovial macrophages as a potential mechanism for TMJOA remission and establishes a targeted nanoplatform for spatial control of joint inflammation.</p> Graphical Abstract <p></p>

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Photothermal reprogramming of synovial M1 macrophages reshapes the pro-inflammatory microenvironment to reverse temporomandibular joint osteoarthritis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月8日

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  • Yanyi Wang,
  • Jiangyan Ren,
  • Tingyu Ren,
  • Baochao Li,
  • Jianchuan Ran,
  • Huijuan Wang,
  • Ziwei Huang,
  • Diya Xie,
  • Tao Liu,
  • Linzhong Yang,
  • Jinglun Zhang,
  • Caixia Zhang,
  • Zhi Wang,
  • Xingyu Luo,
  • Lei Zheng,
  • Xiaoji Xie,
  • Huang Li,
  • Wei Han

摘要

Temporomandibular joint osteoarthritis (TMJOA) involves progressive synovial inflammation-driven cartilage degeneration. While thermotherapy empirically alleviates symptoms, its immunomodulatory mechanism remains elucidated. Here, we revealed that targeted mild hyperthermia reprogramed synovial M1 macrophages via NF-κB pathway suppression, shifting their secretome to attenuate chondrocyte catabolism while enhancing anabolism. This thermally-modified macrophage conditioned medium concurrently promoted osteogenic mineralization. Capitalizing on this, we engineered folic acid-conjugated Y8 nanocomposites (FA-Y8 NPs) for precision M1-targeting photothermal therapy. Under 808 nm irradiation, FA-Y8 NPs achieved localized photothermal reprogramming of synovial M1 macrophages and attenuating cartilage degradation in CFA-induced TMJOA mice. This study reveals thermal immunomodulation of synovial macrophages as a potential mechanism for TMJOA remission and establishes a targeted nanoplatform for spatial control of joint inflammation.

Graphical Abstract