SIRT1 promotes endothelial activity and osteogenesis in vitro and ameliorates age-related skeletal regeneration defects in vivo

Authors

• Shibo Liu, State Key Laboratory of Oral Diseases & National Center for Stomatology &National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
• Jingjing Shao, State Key Laboratory of Oral Diseases & National Center for Stomatology &National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
• Qiheng Yang, State Key Laboratory of Oral Diseases & National Center for Stomatology &National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
• Hanghang Liu, State Key Laboratory of Oral Diseases & National Center for Stomatology &National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China; MaineHealth Institute for Research, Maine Medical Center, Scarborough, ME 04074, USA.

Document Type

Article

Publication Date

9-3-2026

Institution/Department

Center for Molecular Medicine

Journal Title

Stem cell reports

Abstract

Understanding age-driven bone weakening mechanisms is essential for developing precision therapeutic strategies. This study systematically investigated skeletal aging, focusing on the critical decline of SIRT1 and its impact on type H vessels and osteogenic cells. We found that SIRT1 markedly enhanced both endothelial tube formation and osteogenic differentiation in senescent bone marrow-derived mesenchymal stem cell (BMSC)/human umbilical vein endothelial cell (HUVEC) co-cultures. In vivo validation studies revealed that pharmacological activation of SIRT1 significantly improved bone regeneration in age-related osteoporotic defects in both femoral and mandibular sites. Mechanistically, β-catenin served as a downstream mediator of these effects in our experimental systems, with SIRT1 promoting β-catenin deacetylation and nuclear translocation to activate Wnt signaling. By demonstrating that SIRT1 enhances both endothelial and osteogenic functions in the aged bone microenvironment, this work provides a rationale for targeted bone rejuvenation strategies and mechanistically informed therapeutic innovation against geriatric osteoporosis.

First Page

103063

Recommended Citation

Liu, Shibo; Shao, Jingjing; Yang, Qiheng; and Liu, Hanghang, "SIRT1 promotes endothelial activity and osteogenesis in vitro and ameliorates age-related skeletal regeneration defects in vivo" (2026). MaineHealth Maine Medical Center. 4629.
https://knowledgeconnection.mainehealth.org/mmc/4629