2. Academic Validation
  3. BDNF alleviates senescence and enhances osteogenic differentiation in bone marrow mesenchymal stem cells via the TrkB/PI3K/AKT pathway

BDNF alleviates senescence and enhances osteogenic differentiation in bone marrow mesenchymal stem cells via the TrkB/PI3K/AKT pathway

  • Tissue Cell. 2025 May 9:96:102972. doi: 10.1016/j.tice.2025.102972.
Jimei Zhang 1,  Ling Zhu 2,  Jianping Zhou 2,  Qunying Yu 3,  Guangyuan Yang 4,  Chaoli Luo 5,  Jianguo Meng 6,  Shan Xing 7,  Jing Liu 2,  Donggang Mou 8,  Xuming Yang 9
Affiliations

Affiliations

  • 1 Gastroenterology Department, Chenggong Hospital, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan 650505, China.
  • 2 Orthopedics Department, Chenggong Hospital, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan 650505, China.
  • 3 Obstetrics Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, China.
  • 4 Kunming Medical University, Kunming, Yunnan 650500, China.
  • 5 Operating Room, Yunnan Pain Disease Hospital, Kunming, Yunnan 650000, China.
  • 6 Orthopedics Department, Guang Nan Hospital of Traditional Chinese Medicine, Yunnan Province, Guangnan, Yunnan 663300, China.
  • 7 Orthopedics Department, The Second People's Hospital of Yanshan County, Yanshan, Yunnan 663100, China.
  • 8 Pain Department, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan 650055, China.
  • 9 Orthopedics Department, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan 650055, China. Electronic address: yangxmkm@163.com.
PMID: 40367890 DOI: 10.1016/j.tice.2025.102972
Abstract

Background: Bone marrow mesenchymal stem cells (BMSCs) are stem cells that reside in bone marrow and have multidirectional differentiation potential. BMSCs have been used to treat bone injury. However, long-term passage leads to the aging of BMSCs and the weakening of osteogenic differentiation. Furthermore, brain-derived neurotrophic factor (BDNF) may enhance the antiaging ability of BMSCs. The purpose of this study was to investigate the role of BDNF in the senescence and osteogenic differentiation of human BMSCs (hBMSCs).

Methods: The senescence of hBMSCs was induced by successive passages. The mRNA and protein expression levels were measured using RTqPCR and Western blotting. Alkaline Phosphatase (ALP) and alizarin red S (ARS) staining were used to identify osteogenic differentiation in the cells.

Results: After long-term passage, the hBMSCs morphologically gradually expanded and appeared flat, cell viability decreased, the number of fibroblast-like colony-forming units (CFU-Fs) decreased, and the number of β-galactosidase (SA-β-gal)-positive cells and the mRNA expression levels of the senescence-related genes p53, p21 and p16 increased. The activity of ALP, the level of calcium salt deposition and the protein levels of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), Osteopontin (OPN) and BDNF were significantly decreased. Subsequent research indicated that the senescence and inhibition of the osteogenic differentiation of hBMSCs induced by long-term culture were caused by low expression of BDNF. From a mechanistic standpoint, BDNF can activate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway by upregulating the expression of tropomyosin receptor kinase B (TrkB), thereby improving the senescence and inhibition of the osteogenic differentiation of hBMSCs caused by long-term passage.

Conclusion: BDNF improves the senescence and inhibition of the osteogenic differentiation of hBMSCs caused by long-term passage via regulation of the TrkB/PI3K/Akt signaling axis.

Keywords

BDNF; Bone marrow mesenchymal stem cells; Osteogenic differentiation; PI3K/AKT pathway; Senescence; TrkB.

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