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

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-05-09 DOI:10.1016/j.tice.2025.102972

Jimei Zhang , Ling Zhu , Jianping Zhou , Qunying Yu , Guangyuan Yang , Chaoli Luo , Jianguo Meng , Shan Xing , Jing Liu , Donggang Mou , Xuming Yang

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引用次数: 0

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.

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BDNF通过TrkB/PI3K/AKT通路缓解骨髓间充质干细胞衰老，促进成骨分化

骨髓间充质干细胞（bone marrow mesenchymal stem cells, BMSCs）是一种存在于骨髓中的具有多向分化潜能的干细胞。骨髓间充质干细胞已被用于治疗骨损伤。然而，长期传代导致骨髓间充质干细胞老化，成骨分化减弱。此外，脑源性神经营养因子（BDNF）可能增强骨髓间充质干细胞的抗衰老能力。本研究旨在探讨BDNF在人骨髓间充质干细胞（hBMSCs）衰老和成骨分化中的作用。方法采用连续传代法诱导hBMSCs衰老。采用RTqPCR和Western blotting检测mRNA和蛋白表达水平。碱性磷酸酶（ALP）和茜素红S （ARS）染色检测细胞成骨分化。结果长时间传代后，hBMSCs在形态学上逐渐扩大，呈扁平状，细胞活力下降，成纤维细胞样集落形成单位（CFU-Fs）数量减少，β-半乳糖苷酶（SA-β-gal）阳性细胞数量和衰老相关基因p53、p21、p16 mRNA表达水平升高。ALP活性、钙盐沉积水平及矮子相关转录因子2 （RUNX2）、骨钙素（OCN）、骨桥蛋白（OPN）、BDNF蛋白水平均显著降低。随后的研究表明，长期培养诱导的hBMSCs衰老和成骨分化抑制是由BDNF的低表达引起的。从机制上看，BDNF可通过上调原肌球蛋白受体激酶B （TrkB）的表达，激活磷脂酰肌醇3-激酶/蛋白激酶B （PI3K/AKT）通路，从而改善长期传代引起的hBMSCs的衰老和成骨分化抑制。结论bdnf通过调控TrkB/PI3K/AKT信号轴，改善hBMSCs长期传代引起的衰老和成骨分化抑制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.