2. Academic Validation
  3. Aspirin attenuates the detrimental effects of TNF-α on BMMSC stemness by modulating the YAP-SMAD7 axis

Aspirin attenuates the detrimental effects of TNF-α on BMMSC stemness by modulating the YAP-SMAD7 axis

  • Mol Med. 2024 Aug 16;30(1):126. doi: 10.1186/s10020-024-00890-z.
Xudong Wang # 1 2,  Yong Liu # 1 2,  Shiyong Zhang # 1 2,  Linli Zheng 1 2,  Yunze Kang 1 2,  Puyi Sheng 3 4,  Ziji Zhang 5 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, the First Affiliated Hospital of Sun Yat-sen University, #58 Zhongshan Road II, Guangzhou, Guangdong, 510080, China.
  • 2 Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 3 Department of Orthopedics, the First Affiliated Hospital of Sun Yat-sen University, #58 Zhongshan Road II, Guangzhou, Guangdong, 510080, China. shengpy@mail.sysu.edu.cn.
  • 4 Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. shengpy@mail.sysu.edu.cn.
  • 5 Department of Orthopedics, the First Affiliated Hospital of Sun Yat-sen University, #58 Zhongshan Road II, Guangzhou, Guangdong, 510080, China. zhangziji@mail.sysu.edu.cn.
  • 6 Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. zhangziji@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 39152406 DOI: 10.1186/s10020-024-00890-z
Abstract

Background: Bone marrow mesenchymal stem cells (BMMSCs) are commonly used for cell transplantation to treat refractory diseases. However, the presence of inflammatory factors, such as tumour necrosis factor-alpha (TNF-α), at the transplantation site severely compromises the stemness of BMMSCs, thereby reducing the therapeutic effect of cell transplantation. Aspirin (AS) is a drug that has been in use for over a century and has a wide range of effects, including the regulation of cell proliferation, multidirectional differentiation, and immunomodulatory properties of stem cells. However, it is still unclear whether AS can delay the damaging effects of TNF-α on BMMSC stemness.

Methods: This study investigated the effects of AS and TNF-α on BMMSC stemness and the molecular mechanisms using colony formation assay, western blot, qRT-PCR, and overexpression or knockdown of YAP and SMAD7.

Results: The results demonstrated that TNF-α inhibited cell proliferation, the expression of stemness, osteogenic and chondrogenic differentiation markers of BMMSCs. Treatment with AS was shown to mitigate the TNF-α-induced damage to BMMSC stemness. Mechanistic studies revealed that AS may reverse the damage caused by TNF-α on BMMSC stemness by upregulating YAP and inhibiting the expression of SMAD7.

Conclusion: AS can attenuate the damaging effects of TNF-α on BMMSC stemness by regulating the YAP-SMAD7 axis. These findings are expected to promote the application of AS to improve the efficacy of stem cell therapy.

Keywords

Aspirin; BMMSCs; SMAD7; Stemness; TNF-α; YAP.

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