Scholarlink

Background <p>Bone marrow mesenchymal stem cells (BMSCs) play a crucial role in bone repair and regeneration. The sirtuin family member sirtuin 5 (SIRT5) has been implicated in various cellular processes, including the regulation of osteogenic differentiation. This study aimed to investigate the role of SIRT5 in osteogenic differentiation of BMSCs and its impact on fracture healing.</p> Methods <p>BMSCs were characterized and induced to undergo osteogenic and adipogenic differentiation. The effects of SIRT5 modulation on osteogenic differentiation were assessed through alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, and osteogenic genes expression analysis. The role of SIRT5 in regulating bone morphogenetic protein 2 (BMP2) succinylation and stability was explored using Western blot, immunoprecipitation, and co-immunoprecipitation. A rat tibial fracture model was used to evaluate the in vivo effects of SIRT5 and BMP2 modulation on fracture healing, assessed by Micro-CT and histological analysis.</p> Results <p>SIRT5 overexpression enhanced osteogenic differentiation of BMSCs, as evidenced by increased ALP activity and mineralization. It also upregulated the expression of osteogenic markers such as osteopontin (OPN), runt-related transcription factor 2 (RUNX2), osterix (OSX), and BMP2. Conversely, SIRT5 knockdown inhibited these processes. Mechanistically, SIRT5 was found to regulate BMP2 succinylation, affecting its stability and function. In vivo, overexpression of SIRT5 in a rat tibial fracture model significantly improved bone volume fraction, trabecular number, and thickness, while reducing trabecular separation. The beneficial effects of SIRT5 overexpression were counteracted by BMP2 knockdown, highlighting the importance of BMP2 in mediating SIRT5’s actions on bone healing.</p> Conclusion <p>SIRT5 promotes osteogenic differentiation of BMSCs and enhances fracture healing by modulating BMP2 succinylation. These findings suggest that SIRT5 could be a potential therapeutic target for the treatment of bone fractures and other skeletal disorders.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

SIRT5-mediated regulation of BMP2 succinylation enhances osteogenic differentiation of BMSCs and promotes tibial fracture healing

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月24日

查看全文
  • Hongji Gu,
  • Buhan Liu,
  • Yue An

摘要

Background

Bone marrow mesenchymal stem cells (BMSCs) play a crucial role in bone repair and regeneration. The sirtuin family member sirtuin 5 (SIRT5) has been implicated in various cellular processes, including the regulation of osteogenic differentiation. This study aimed to investigate the role of SIRT5 in osteogenic differentiation of BMSCs and its impact on fracture healing.

Methods

BMSCs were characterized and induced to undergo osteogenic and adipogenic differentiation. The effects of SIRT5 modulation on osteogenic differentiation were assessed through alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, and osteogenic genes expression analysis. The role of SIRT5 in regulating bone morphogenetic protein 2 (BMP2) succinylation and stability was explored using Western blot, immunoprecipitation, and co-immunoprecipitation. A rat tibial fracture model was used to evaluate the in vivo effects of SIRT5 and BMP2 modulation on fracture healing, assessed by Micro-CT and histological analysis.

Results

SIRT5 overexpression enhanced osteogenic differentiation of BMSCs, as evidenced by increased ALP activity and mineralization. It also upregulated the expression of osteogenic markers such as osteopontin (OPN), runt-related transcription factor 2 (RUNX2), osterix (OSX), and BMP2. Conversely, SIRT5 knockdown inhibited these processes. Mechanistically, SIRT5 was found to regulate BMP2 succinylation, affecting its stability and function. In vivo, overexpression of SIRT5 in a rat tibial fracture model significantly improved bone volume fraction, trabecular number, and thickness, while reducing trabecular separation. The beneficial effects of SIRT5 overexpression were counteracted by BMP2 knockdown, highlighting the importance of BMP2 in mediating SIRT5’s actions on bone healing.

Conclusion

SIRT5 promotes osteogenic differentiation of BMSCs and enhances fracture healing by modulating BMP2 succinylation. These findings suggest that SIRT5 could be a potential therapeutic target for the treatment of bone fractures and other skeletal disorders.