Stem cell secretome restore the adipo-osteo differentiation imbalance in diabetic dental pulp-derived mesenchymal stem cells

Q1 Medicine Chronic Diseases and Translational Medicine Pub Date : 2024-05-06 DOI:10.1002/cdt3.125

Avinash Sanap, Kalpana Joshi, Supriya Kheur, Ramesh Bhonde

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Abstract

Background

Mesenchymal stem cells (MSCs) from type 2 diabetes mellitus (T2DM) individuals exhibit increased adipogenesis and decreased osteogenesis. We investigated the potential of adipose tissue-derived MSCs (ADMSCs) secretome obtained from healthy individuals in restoring the tumor necrosis factor-α (TNF-α) mediated imbalance in the adipo/osteogenic differentiation in the dental pulp-derived MSCs obtained from T2DM individuals (dDPMSCs).

Methods

dDPMSCs were differentiated into adipocytes and osteocytes using a standard cocktail in the presence of (a) induction cocktail, (b) induction cocktail + TNF-α, and (c) induction cocktail+ TNF-α + ADMSCs-secretome (50%) for 15 and 21 days resp. Differentiated adipocytes and osteocytes were stained by oil red O and alizarin red and analyzed by using ImageJ software. Molecular expression of the key genes involved was analyzed by using reverse-transcription polymerase chain reaction (RT-PCR).

Results

Treatment of TNF-α augmented the adipogenesis (9571 ± 765 vs. 19,815 ± 1585 pixel, p < 0.01) and decreased the osteogenesis (15,603 ± 1248 vs. 11,894 ± 951 pixel, p < 0.05) of dDPMSCs as evidenced by the oil red O and alizarin red staining respectively. Interestingly, dDPMSCs differentiated along with TNF-α and 50% ADMSCs secretome exhibited enhanced osteogenesis (11,894 ± 951 vs. 41,808 ± 3344 pixel, p < 0.01) and decreased adipogenesis (19,815 ± 1585 vs. 4480 ± 358 pixel, p < 0.01). Additionally, dDPMSCs differentiated along with ADMSCs secretome exhibited decreased expression of PPARg (p < 0.01), C/EBPa (p < 0.05), and FAS (p < 0.01) whereas mRNA expression of Runx2 (p < 0.05), Osterix (p < 0.01), and OCN (p < 0.05) was upregulated as revealed by the RT-PCR analysis.

Conclusion

ADMSCs secretome from healthy individuals restore the TNF-α influenced differentiation fate of dDPMSCs and therefore can be explored for T2DM clinical management in the future.

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干细胞分泌物可恢复糖尿病牙髓间充质干细胞的脂肪-骨骼分化失衡

来自2型糖尿病（T2DM）患者的间充质干细胞（MSCs）表现出脂肪生成增加和骨生成减少。我们研究了从健康人体内获得的脂肪组织间充质干细胞（ADMSCs）分泌组在恢复T2DM患者牙髓间充质干细胞（dDPMSCs）中肿瘤坏死因子-α（TNF-α）介导的脂肪/成骨分化失衡方面的潜力。在(a)诱导鸡尾酒、(b)诱导鸡尾酒+TNF-α和(c)诱导鸡尾酒+TNF-α+ADMSCs-分泌物（50%）存在下，使用标准鸡尾酒将dDPMSCs分化成脂肪细胞和骨细胞，分别持续15天和21天。油红 O 和茜素红染色分别显示，TNF-α 可促进 dDPMSCs 的脂肪生成（9571 ± 765 vs. 19815 ± 1585 像素，p < 0.01）和骨生成（15603 ± 1248 vs. 11894 ± 951 像素，p < 0.05）。有趣的是，与 TNF-α 和 50% ADMSCs 分泌物一起分化的 dDPMSCs 表现出骨生成增强（11,894 ± 951 vs. 41,808 ± 3344 像素，p < 0.01）和脂肪生成减少（19,815 ± 1585 vs. 4480 ± 358 像素，p < 0.01）。此外，与 ADMSCs 分泌物一起分化的 dDPMSCs 表现出 PPARg（p < 0.01）、C/EBPa（p < 0.05）和 FAS（p < 0.01）的表达减少，而 Runx2（p < 0.05）、Osterix（p < 0.RT-PCR分析表明，健康人的ADMSCs分泌组恢复了TNF-α对dDPMSCs分化命运的影响，因此可在未来的T2DM临床治疗中进行探索。

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来源期刊

Chronic Diseases and Translational Medicine Medicine-General Medicine

CiteScore

6.70

自引率

0.00%

发文量

195

审稿时长

35 weeks

期刊介绍： This journal aims to promote progress from basic research to clinical practice and to provide a forum for communication among basic, translational, and clinical research practitioners and physicians from all relevant disciplines. Chronic diseases such as cardiovascular diseases, cancer, diabetes, stroke, chronic respiratory diseases (such as asthma and COPD), chronic kidney diseases, and related translational research. Topics of interest for Chronic Diseases and Translational Medicine include Research and commentary on models of chronic diseases with significant implications for disease diagnosis and treatment Investigative studies of human biology with an emphasis on disease Perspectives and reviews on research topics that discuss the implications of findings from the viewpoints of basic science and clinical practic.

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