Low Magnitude of Compression Enhances Biosynthesis of Mesenchymal Stem Cells towards Nucleus Pulposus Cells via the TRPV4-Dependent Pathway.
Low Magnitude of Compression Enhances Biosynthesis of Mesenchymal Stem Cells towards Nucleus Pulposus Cells via the TRPV4-Dependent Pathway.
复制标题
低强度压缩可通过 TRPV4 依赖性途径增强间充质干细胞向髓核细胞的生物合成
DOI：
10.1155/2018/7061898
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发表时间：
2018
影响因子：
4.3
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Gan Y;Tu B;Li P;Ye J;Zhao C;Luo L;Zhang C;Zhang Z;Zhu L;Zhou Q
间充质干细胞（MSC）为基础的治疗被认为是一个有前途的组织工程策略，实现髓核（NP）再生治疗椎间盘退变（IDD）。然而，促进MSC的生物合成以满足NP再生的需要仍然是一个挑战。本研究的目的是优化压缩的幅度，以提高细胞外基质（ECM）的沉积对骨髓间充质干细胞的椎间盘形成。因此，我们构建了一个3D培养模型的MSC承受不同程度的压缩7天（5%，10%和20%，频率为1.0 Hz，8小时/天），使用智能和机械活性生物反应器。进一步探讨了瞬时受体电位香草酸4（TRPV 4）的力学信号转导机制。通过Live/Dead染色、生化含量测定、实时荧光定量PCR、Western blot、组织学和免疫组织化学分析对包封的MSC进行评价。结果表明，低幅度的压缩促进合成代谢反应，而高幅度的压缩诱导3D培养的MSC的分解代谢反应。抑制TRPV 4可抑制低强度压迫的合成代谢作用。同时，TRPV 4的激活增强了类似于低幅度压缩的生物合成。这些发现表明，低幅度的压缩促进了ECM沉积对3D培养的MSC的椎间盘形成的合成代谢反应，并且TRPV 4通道在低幅度压缩载荷的机械信号转导中起关键作用。对这一机制的进一步了解可能为基于MSC的NP再生的新疗法的开发提供见解。
Mesenchymal stem cell- (MSC-) based therapy is regarded as a promising tissue engineering strategy to achieve nucleus pulposus (NP) regeneration for the treatment of intervertebral disc degeneration (IDD). However, it is still a challenge to promote the biosynthesis of MSC to meet the requirement of NP regeneration. The purpose of this study was to optimize the compressive magnitude to enhance the extracellular matrix (ECM) deposition towards discogenesis of MSCs. Thus, we constructed a 3D culture model for MSCs to bear different magnitudes of compression for 7 days (5%, 10%, and 20% at the frequency of 1.0 Hz for 8 hours/day) using an intelligent and mechanically active bioreactor. Then, the underlying mechanotransduction mechanism of transient receptor potential vanilloid 4 (TRPV4) was further explored. The MSC-encapsulated hybrids were evaluated by Live/Dead staining, biochemical content assay, real-time PCR, Western blot, histological, and immunohistochemical analysis. The results showed that low-magnitude compression promoted anabolic response where high-magnitude compression induced the catabolic response for the 3D-cultured MSCs. The anabolic effect of low-magnitude compression could be inhibited by inhibiting TRPV4. Meanwhile, the activation of TRPV4 enhanced the biosynthesis analogous to low-magnitude compression. These findings demonstrate that low-magnitude compression promoted the anabolic response of ECM deposition towards discogenesis for the 3D-cultured MSCs and the TRPV4 channel plays a key role on mechanical signal transduction for low-magnitude compressive loading. Further understanding of this mechanism may provide insights into the development of new therapies for MSC-based NP regeneration.