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CH-M6P能否成为骨再生的潜在双功能候选物?

Could CH-M6P Be a Potential Dual-Functioning Candidate for Bone Regeneration?

作者信息

Huseynova Fidan, Ionescu Cătălina, Cuisinier Frederic, Huseynova Irada, Mammadov Alamdar, Barragan-Montero Véronique

机构信息

LBN, Montpellier University, 34193 Montpellier, France.

Institute of Molecular Biology and Biotechnologies, Minstry of Science and Education of the Republic of Azerbaian, AZ1073 Baku, Azerbaijan.

出版信息

Biomedicines. 2024 Nov 26;12(12):2697. doi: 10.3390/biomedicines12122697.

Abstract

: CI-RM6P has different binding sites with affinities for both M6P and IGF2, plays a role in the regulation of the TGF-β and IGF pathways that is important for controlling cell growth and differentiation. We hypothesize that previously synthesised derivative of M6P could be an alternative candidate for bone tissue regeneration in terms of higher binding affinity, stability in human serum, low cost and temporal delivery. : CH-M6P is synthesised based on previously described protocol; mesenchymal origin of isolated DPSCs was assessed by flow cytometry and AR staining prior to alkaline phosphatase (ALP) activity test, qPCR to evaluate differentiation specific marker expression, immunofluoresence, and SEM/EDS to evaluate organic and inorganic matrix formation; and rat aortic ring model to evaluate angiogenic effect of molecule. : CH-M6P upregulated ALP activity, the expression of the , , , , , , , and genes under osteogenic conditions. The results of immunofluorescence and SEM/EDS studies did not show enhancing effect on matrix formation. As we observed, the induction effect of CH-M6P on the expression of angiogenic genes such as and , even under osteogenic conditions, within the scope of research, we checked the angiogenic effect of the molecule and compared it to VEGF, showing that the CH-M6P is really angiogenic. : Our findings provide an important clue for the further exploration of the molecule, which can be necessary to enhance the capability of the commonly used osteomedium, possibly leading to the development of bone-forming drugs and has the potential to be a dual-functioning molecule for bone tissue engineering.

摘要

CI-RM6P对M6P和IGF2具有不同的结合位点及亲和力,在TGF-β和IGF信号通路的调节中发挥作用,这对控制细胞生长和分化至关重要。我们推测,就更高的结合亲和力、在人血清中的稳定性、低成本及缓释性而言,先前合成的M6P衍生物可能是骨组织再生的替代候选物。CH-M6P是根据先前描述的方案合成的;在进行碱性磷酸酶(ALP)活性测试、评估分化特异性标志物表达的qPCR、免疫荧光以及评估有机和无机基质形成的扫描电子显微镜/能谱分析(SEM/EDS)之前,通过流式细胞术和AR染色评估分离的牙髓干细胞的间充质来源;并采用大鼠主动脉环模型评估该分子的血管生成作用。CH-M6P在成骨条件下上调了ALP活性以及、、、、、、和基因的表达。免疫荧光和SEM/EDS研究结果未显示对基质形成有增强作用。如我们所观察到的,即使在成骨条件下,CH-M6P对血管生成基因如和的表达也有诱导作用,在本研究范围内,我们检测了该分子的血管生成作用并将其与VEGF进行比较,结果表明CH-M6P确实具有血管生成作用。我们的研究结果为该分子的进一步探索提供了重要线索,这对于增强常用骨培养基的能力可能是必要的,可能会促成成骨药物的开发,并且有可能成为骨组织工程的双功能分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06ee/11673785/43134621ebc8/biomedicines-12-02697-sch001.jpg

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