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  2. The SIRT1 activator SRT2104 promotes BMP9-induced osteogenic and angiogenic differentiation in mesenchymal stem cells

The SIRT1 activator SRT2104 promotes BMP9-induced osteogenic and angiogenic differentiation in mesenchymal stem cells

  • Mech Ageing Dev. 2022 Oct;207:111724. doi: 10.1016/j.mad.2022.111724.
Yang Lu 1 Zhao-Xin Ma 2 Rui Deng 1 Hai-Tao Jiang 1 Lei Chu 3 Zhong-Liang Deng 4
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
  • 2 Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong, Chongqing 400016, China.
  • 3 Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China. Electronic address: Chulei2380@163.com.
  • 4 Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China. Electronic address: dengzl@cqmu.edu.cn.
Abstract

Bone defects resulting from trauma, bone tumors, infections and skeletal abnormalities are a common osteoporotic condition with respect to clinical treatment. Of the known bone morphogenetic proteins (BMPs), BMP9 has the strongest osteogenic differentiation potential, which could be beneficial in the construction of tissue-engineered bone. Silent mating type information regulator 2 homolog-1 (SIRT1) is a highly conserved nicotinamide adenine dinucleotide-dependent deacetylase that deacetylates and modulates histone or non-histone substrates. However, the role of SIRT1 in BMP9-induced osteogenic differentiation of stem cells has not been studied. Furthermore, it is unclear whether SIRT1 interacts with the BMP/Smad and BMP/MAPK pathways in stem cells. We found that SIRT1 expression decreased gradually in a time-dependent manner during BMP9-induced osteogenic differentiation of MSCs. Interactions between SIRT1 and Smad7 promoted degradation of Smad7 and increased Smad1/5/8 phosphorylation. SRT2104, an activator of SIRT, enhanced the expression of osteogenic- and angiogenic-related proteins in BMP9-induced MSCs. In addition, we found that activation of the BMP/MAPK pathway led to osteogenic and angiogenic differentiation of MSCs. Our study demonstrated that SIRT1 expression decreased during BMP9-induced differentiation. The SIRT1 Activator SRT2104 promoted BMP9-induced osteogenic and angiogenic differentiation of MSCs through the BMP/Smad and BMP/MAPK signaling pathways.

Keywords

Angiogenic differentiation; BMP9; MSCs; Osteogenic differentiation; SIRT1.

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