2. Academic Validation
  3. Matrix stiffness regulates macrophage polarisation via the Piezo1-YAP signalling axis

Matrix stiffness regulates macrophage polarisation via the Piezo1-YAP signalling axis

  • Cell Prolif. 2024 Mar 31:e13640. doi: 10.1111/cpr.13640.
Feng Mei 1 2 3,  Yaru Guo 4,  Yu Wang 5,  Yingying Zhou 6,  Boon Chin Heng 7,  Mengru Xie 1 2 3,  Xiaofei Huang 1 2 3,  Shihan Zhang 4,  Shuai Ding 5,  Fangyong Liu 6,  Xuliang Deng 4 6,  Lili Chen 1 2 3,  Cheng Yang 1 2 3
Affiliations

Affiliations

  • 1 Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China.
  • 4 Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
  • 5 Department of Orthodontics, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China.
  • 6 NMPA Key Laboratory for Dental Materials, Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, China.
  • 7 Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
PMID: 38556840 DOI: 10.1111/cpr.13640
Abstract

Macrophages play a pivotal role in the immunological cascade activated in response to biomedical implants, which predetermine acceptance or rejection of implants by the host via pro- and anti-inflammatory polarisation states. The role of chemical signals in macrophage polarisation is well-established, but how physical cues regulate macrophage function that may play a fundamental role in implant-bone interface, remains poorly understood. Here we find that bone marrow-derived macrophages (BMDM) cultured on polyacrylamide gels of varying stiffness exhibit different polarisation states. BMDM are 'primed' to a pro-inflammatory M1 phenotype on stiff substrates, while to an anti-inflammatory M2 phenotype on soft and medium stiffness substrates. It is further observed that matrix stiffening increases Piezo1 expression, as well as leads to subsequent activation of the mechanotransduction signalling effector YAP, thus favouring M1 polarisation whilst suppressing M2 polarisation. Moreover, upon treatment with YAP Inhibitor, we successfully induce macrophage re-polarisation to the M2 state within the implant site microenvironment, which in turn promotes implant osseointegration. Collectively, our present study thus characterises the critical role of the Piezo1-YAP signalling axis in macrophage mechanosensing and stiffness-mediated macrophage polarisation and provides cues for the design of immuno-modulatory biomaterials that can regulate the macrophage phenotype.

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