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Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing.
Zou, Nan-Yu; Liu, Ran; Huang, Mei; Jiao, Yu-Rui; Wei, Jie; Jiang, Yangzi; He, Wen-Zhen; Huang, Min; Xu, Yi-Li; Liu, Ling; Sun, Yu-Chen; Yang, Mi; Guo, Qi; Huang, Yan; Su, Tian; Xiao, Ye; Wang, Wei-Shan; Zeng, Chao; Lei, Guang-Hua; Luo, Xiang-Hang; Li, Chang-Jun.
Afiliación
  • Zou NY; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Liu R; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Huang M; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Jiao YR; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Wei J; Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Jiang Y; Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China.
  • He WZ; Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, Hunan, 410008, China.
  • Huang M; Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University, Changsha, China.
  • Xu YL; School of Biomedical Sciences, Institute for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Liu L; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Sun YC; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Yang M; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Guo Q; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Huang Y; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Su T; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Xiao Y; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Wang WS; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Zeng C; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Lei GH; Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • Luo XH; Department of Orthopaedics, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, China.
  • Li CJ; Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
Bone Res ; 12(1): 6, 2024 01 25.
Article en En | MEDLINE | ID: mdl-38267422
ABSTRACT
Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Callosidades / Fracturas Óseas Límite: Aged / Animals / Humans Idioma: En Revista: Bone Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: China
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Callosidades / Fracturas Óseas Límite: Aged / Animals / Humans Idioma: En Revista: Bone Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: China