2. Academic Validation
  3. Lactate Accelerates Early Angiogenesis and Bone Regeneration Through Macrophage M1 Polarisation

Lactate Accelerates Early Angiogenesis and Bone Regeneration Through Macrophage M1 Polarisation

  • Cell Prolif. 2026 Jan 26:e70177. doi: 10.1111/cpr.70177.
Lulu Liu 1,  Danning Ma 1,  Jia Song 2,  Boon Chin Heng 2,  Ying Huang 3,  Xuehui Zhang 2,  Mingming Xu 3,  Yan Wei 3,  Tai Wei 1,  Jinqi Wei 1,  Xuliang Deng 3
Affiliations

Affiliations

  • 1 First Clinical Division, Peking University School and Hospital of Stomatology and National Center of Stomatology and National Clinical Research Center for Oral Diseases and National Engineering Research Center of Oral Biomaterials and Digital Stomatology and Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health and NMPA Key Laboratory for Dental Materials, Beijing, People's Republic of China.
  • 2 Department of Dental Materials, Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology and National Center of Stomatology and National Clinical Research Center for Oral Diseases and National Engineering Research Center of Oral Biomaterials and Digital Stomatology and Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health and NMPA Key Laboratory for Dental Materials, Beijing, People's Republic of China.
  • 3 Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology and National Center of Stomatology and National Clinical Research Center for Oral Diseases and National Engineering Research Center of Oral Biomaterials and Digital Stomatology and Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health and NMPA Key Laboratory for Dental Materials, Beijing, People's Republic of China.
PMID: 41587535 DOI: 10.1111/cpr.70177
Abstract

Failure of timely bone regeneration compromises structural integrity and delays functional recovery; therefore immune regulation of the early repair microenvironment is crucial for successful healing. M1 (pro-inflammatory) phenotype macrophages play pivotal roles in vascularisation during the early phase of bone regeneration and are typically activated by interferon-gamma (IFN-γ) or lipopolysaccharide (LPS) as well as by metabolite-derived signals. Lactate, a metabolite known to regulate a series of pathophysiological processes, has not yet been fully investigated for its specific immunomodulatory role in the microenvironment of bone injury healing. Our in vitro experiments demonstrated that lactate induced macrophage polarisation to the M1 phenotype and accelerated angiogenesis, with the HIF1α-NOD1-calcium influx axis identified as a key mediator. In vivo validation further confirmed the positive effects of lactate intervention in promoting vascularised bone regeneration at the early stage of injury. Thus, this study uncovers how lactate modulates immune response in association with M1 macrophages and indicates its potential as a therapeutic strategy for promoting vascularised bone healing.

Keywords

M1 polarisation; angiogenesis; bone regeneration; lactate; macrophages.

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