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使君子科植物钟萼木树皮提取物:通过激活脂肪间充质干细胞中的 Wnt/β-连环蛋白通路促进成骨。

Butea monosperma bark extract: a natural boost for osteogenesis via Wnt/β-catenin pathway activation in adipose-derived mesenchymal stem cells.

机构信息

Advanced Centre for Tissue Engineering, Department of Biochemistry, University of Kerala, Kariavattom, Trivandrum, Kerala, 695581, India.

Centre of Excellence in Stem Cell Research, Division of Biotechnology, Karunya Institute of Technology and Sciences, Coimbatore, Tamil Nadu, 641114, India.

出版信息

Biotechnol Lett. 2024 Nov 25;47(1):3. doi: 10.1007/s10529-024-03545-5.

Abstract

PURPOSE

To investigate the impact of Butea monosperma (BM) bark extract on the osteogenic differentiation potential of rat adipose-derived mesenchymal stem cells (rADMSCs) and to elucidate the involvement of Wnt/β-catenin pathway in mediating this osseous effect.

METHODS

Characterizations (antioxidant assays, FTIR and LC/MS analyses) and docking studies (in silico) were performed to evaluate the presence of phytochemicals in the BM extract and their binding capacity to that of the frizzled receptor. rADMSCs were isolated and characterised for its differentiation potential of osteogenesis for stemness. Dose fixation, cytotoxicity, osteogenic differentiation (calcium, mineral deposition, alkaline phosphatase and osteocalcin) and gene expression (osteocalcin, Col1, osteonectin, Bmp2, Runx2, Wnt2, and β-catenin-14 and 28 days) of the extract were also evaluated in vitro.

RESULTS

FTIR and LC/MS analyses unveiled the phytochemicals in the extract and with docking studies confirmed their interaction with the frizzled receptor of Wnt/β-catenin pathway. rADMSCs were isolated and differentiated in the presence of the osteogenic induction medium. Dose fixation studies, cytotoxicity and cell viability assessments demonstrated the phytochemicals concentration-dependent cytotoxicity. The presence of specific bone markers highlighted the osteogenic differentiation potential of the phytochemicals. Furthermore, gene expression studies of rADMSCs depicted a heightened bone-forming capacity potentially facilitated by the activation of Wnt/β-catenin pathway.

CONCLUSION

The phytochemicals of BM promoted the osteogenic differentiation of rADMSCs through the activation of the signalling Wnt/β-Catenin pathway, as evidenced by the significant upregulation of early and late bone markers. The phytochemicals may therefore be positioned as promising therapeutic agents for enhancing bone regeneration, offering new avenues for regenerative medicine.

摘要

目的

研究补骨脂(Butea monosperma,BM)树皮提取物对大鼠脂肪间充质干细胞(rADMSCs)成骨分化潜能的影响,并阐明 Wnt/β-catenin 通路在介导这种成骨性作用中的作用。

方法

进行特征描述(抗氧化测定、FTIR 和 LC/MS 分析)和对接研究(计算机模拟),以评估 BM 提取物中植物化学物质的存在及其与卷曲受体结合的能力。rADMSCs 被分离并鉴定其成骨分化潜能。还评估了提取物的剂量固定、细胞毒性、成骨分化(钙、矿物质沉积、碱性磷酸酶和骨钙素)和基因表达(骨钙素、Col1、骨粘连蛋白、Bmp2、Runx2、Wnt2 和β-catenin-14 和 28 天)。

结果

FTIR 和 LC/MS 分析揭示了提取物中的植物化学物质,并通过对接研究证实了它们与 Wnt/β-catenin 通路的卷曲受体的相互作用。rADMSCs 在存在成骨诱导培养基的情况下被分离和分化。剂量固定研究、细胞毒性和细胞活力评估表明,植物化学物质的浓度具有细胞毒性。特定骨标志物的存在突出了植物化学物质的成骨分化潜力。此外,rADMSCs 的基因表达研究表明,Wnt/β-catenin 通路的激活增强了骨形成能力。

结论

BM 的植物化学物质通过激活信号 Wnt/β-Catenin 通路促进 rADMSCs 的成骨分化,这可以从早期和晚期骨标志物的显著上调得到证明。因此,植物化学物质可能被定位为增强骨再生的有前途的治疗剂,为再生医学提供了新的途径。

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