2. Academic Validation
  3. miR-203-3p promotes senescence of mouse bone marrow mesenchymal stem cells via downregulation of Pbk

miR-203-3p promotes senescence of mouse bone marrow mesenchymal stem cells via downregulation of Pbk

  • Aging Cell. 2024 Aug 9:e14293. doi: 10.1111/acel.14293.
Qiaojuan Mei 1,  Kexin Li 1,  Tianyu Tang 1,  Siying Cai 1,  Yu Liu 1 2,  Xiaofei Wang 1 3,  Yinzhao Jia 4,  Ling Zhang 1,  Huaibiao Li 1,  Hui Song 5,  Jun Zhai 6,  Wenpei Xiang 1
Affiliations

Affiliations

  • 1 Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Gynecology, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.
  • 3 The First College of Clinical Medical Science, China Three Gorges University, Yichang, China.
  • 4 Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Department of Cardiology, Jinan Central Hospital, Shandong First Medical University, Jinan, Shandong, China.
  • 6 Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
PMID: 39123275 DOI: 10.1111/acel.14293
Abstract

The senescence of bone marrow mesenchymal stem cells (BMSCs) contributes to the development of degenerative skeletal conditions. To date, the molecular mechanism resulting in BMSC senescence has not been fully understood. In this study, we identified a small non-coding RNA, miR-203-3p, the expression of which was elevated in BMSCs from aged mice. On the Other hand, overexpression of miR-203-3p in BMSCs from young mice reduced cell growth and enhanced their senescence. Mechanistically, PDZ-linked kinase (PBK) is predicted to be the target of miR-203-3p. The binding of miR-203-3p to Pbk mRNA could decrease its expression, which in turn inhibited the ubiquitination-mediated degradation of p53. Furthermore, the intravitreal injection of miR-203-3p-inhibitor into the bone marrow cavity of aged mice attenuated BMSC senescence and osteoporosis in aged mice. Collectively, these findings suggest that targeting miR-203-3p to delay BMSC senescence could be a potential therapeutic strategy to alleviate age-related osteoporosis.

Keywords

PDZ‐binding kinase; aging; bone marrow mesenchymal stem cells; miR‐203‐3p; osteoporosis.

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