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Ciliotherapy Treatments to Enhance Biochemically- and Biophysically-Induced Mesenchymal Stem Cell Osteogenesis: A Comparison Study.
Cellular and Molecular Bioengineering ( IF 2.8 ) Pub Date : 2018-11-20 , DOI: 10.1007/s12195-018-00561-0
M A Corrigan 1, 2 , T M Ferradaes 1, 2, 3 , M Riffault 1, 2, 4 , D A Hoey 1, 2, 4
Affiliation  

Introduction

New approaches to treat osteoporosis have focused on promoting bone formation through the targeting of osteoblasts and their progenitors, mesenchymal stem cells (MSCs). The primary cilium is a singular cellular extension known to play an important role in biochemical and biophysical osteogenic induction of MSCs. Defects in ciliary structure have been associated with a plethora of diseases. Therefore targeting the cilium therapeutically (ciliotherapies) has emerged as a potential new treatment modality. Therefore, this study performed a comparison analysis on known ciliotherapies and their potential effects in mediating MSC osteogenic differentiation.

Methods

MSCs were treated with forskolin, lithium chloride (LiCl) or fenoldopam to investigate the effect on ciliogenesis and cilia-associated signalling. Moreover, both early and long term biochemical and biophysical (fluid shear) induced osteogenic differentiation was examined in terms of osteogenic gene expression and bone matrix deposition following each treatment.

Results

LiCl and fenoldopam were found to enhance MSC ciliogenesis to a similar degree. LiCl significantly altered hedgehog (HH) and Wnt signalling which was associated with inhibited osteogenic gene expression, while fenoldopam demonstrated enhanced early osteogenesis. Long term treatment with both ciliotherapies did not enhance osteogenesis, however LiCl had detrimental effects on cell viability. Intriguingly both ciliotherapies enhanced MSC mechanosensitivity as demonstrated by augmented osteogenic gene expression in response to fluid shear, which over longer durations resulted in enhanced matrix deposition per cell.

Conclusions

Therefore, ciliotherapies can be utilised to enhance MSC ciliogenesis resulting in enhanced mechanosensitivity, however, only fenoldopam is a viable ciliotherapeutic option to enhance MSC osteogenesis.


中文翻译:

Ciliotherapy 治疗以增强生化和生物物理诱导的间充质干细胞成骨:比较研究。

介绍

治疗骨质疏松症的新方法集中在通过靶向成骨细胞及其祖细胞间充质干细胞 (MSCs) 促进骨形成。初级纤毛是一种单一的细胞延伸,已知在 MSCs 的生化和生物物理成骨诱导中起重要作用。睫状结构缺陷与多种疾病有关。因此,治疗性靶向纤毛(纤毛疗法)已成为一种潜在的新治疗方式。因此,本研究对已知纤毛疗法及其在介导MSC成骨分化中的潜在作用进行了比较分析。

方法

MSCs 用毛喉素、氯化锂 (LiCl) 或非诺多泮处理,以研究对纤毛发生和纤毛相关信号传导的影响。此外,根据每次治疗后的成骨基因表达和骨基质沉积,检查了早期和长期生化和生物物理(流体剪切)诱导的成骨分化。

结果

发现 LiCl 和非诺多泮以相似的程度增强 MSC 纤毛发生。LiCl 显着改变了与抑制成骨基因表达相关的hedgehog (HH) 和Wnt 信号传导,而非诺多泮表现出增强的早期成骨作用。两种纤毛疗法的长期治疗并没有增强成骨,但是 LiCl 对细胞活力有不利影响。有趣的是,两种纤毛疗法都增强了 MSC 的机械敏感性,这可以通过响应流体剪切的成骨基因表达增强来证明,这在更长的时间内导致每个细胞的基质沉积增强。

结论

因此,纤毛疗法可用于增强 MSC 纤毛发生,从而提高机械敏感性,然而,只有非诺多泮是增强 MSC 成骨的可行纤毛治疗选择。
更新日期:2018-11-20
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