• Tai Wei, Danning Ma, Lulu Liu, Ying Huang, Xuehui Zhang, Mingming Xu, Yan Wei, Jinqi Wei, and Xuliang Deng.
• First Clinical Division, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, No.37A, Xishiku Avenue, Xicheng District, Beijing, 100034, PR China.
• Transl Res. 2024 Nov 1; 273: 788978-89.

AbstractBone malunion or nonunion leads to functional and esthetic problems and is a major healthcare burden. Activation of bone marrow mesenchymal stem cells (BMSCs) and subsequent induction of osteogenic differentiation by local metabolites are crucial steps for bone healing, which has not yet been completely investigated. Here, we found that lactate levels are rapidly increased at the local injury site during the early phase of bone defect healing, which facilitates the healing process by enhancing BMSCs regenerative capacity. Mechanistically, lactate serves as a ligand for the Olfr1440 olfactory receptor, to trigger an intracellular calcium influx that in turn activates osteogenic phenotype transition of BMSCs. Conversely, ablation of Olfr1440 delays skeletal repair and remodelling, as evidenced by thinner cortical bone and less woven bone formation in vivo. Administration of lactate in the defect area enhanced bone regeneration. These findings thus revealed the key roles of lactate in the osteogenic differentiation of BMSCs, which deepened our understanding of the bone healing process, as well as provided cues for a potential therapeutic option that might greatly improve bone defect treatment.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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