Modulation of sirtuins during monolayer chondrocyte culture influences cartilage regeneration upon transfer to a 3D culture environment.
Modulation of sirtuins during monolayer chondrocyte culture influences cartilage regeneration upon transfer to a 3D culture environment.
复制标题
单层软骨细胞培养过程中Sirtuins的调节会影响软骨再生3D培养环境。
DOI：
10.3389/fbioe.2022.971932
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发表时间：
2022
影响因子：
5.7
通讯作者：
Lee, David A. A.
中科院分区：
文献类型：
--
作者：
Heywood, Hannah K. K.;Thorpe, Stephen D. D.;Jeropoulos, Renos M. M.;Caton, Paul W. W.;Lee, David A. A.
关键词：
本研究探讨了sirtuins在关节软骨细胞再生潜能中的作用。Sirtuins(SIRT1-7)在调节软骨内稳态方面起着关键作用。通过抑制导致软骨降解的促炎途径和促进关键基质成分的表达，sirtuins有可能在对再生医学至关重要的合成代谢和分解代谢过程之间实现有利的平衡。当受到代表体内生态位的渗透压和葡萄糖浓度时，新鲜分离的牛软骨细胞SIRT1基因表达增加，但SIRT3基因表达没有增加。采用复制方法体外单层扩增软骨细胞，用于软骨再生治疗，我们发现SIRT1基因在扩增过程中表达下降。在体外扩增过程中，通过添加SIRT1特异性激活剂SRT1720、烟酰胺单核苷酸或泛sirtuin抑制剂烟酰胺来控制sirtuin的活性，显著影响了随后3D培养中的软骨再生。在扩张过程中，由于sirtuin的抑制，组织质量、细胞密度和细胞外基质含量减少，而sirtuin的激活加强了这些软骨组织再生的措施。单层扩张过程中sirtuin活性的调节影响了H3K27me3，这是一个在发育和分化中具有重要作用的异染色质标记。出乎意料的是，在3D培养中用sirtuin激活剂处理原代软骨细胞会减少它们的基质合成。因此，在体外单层扩张阶段调节sirtuin活性可能代表着一个独特的机会来提高软骨再生医学技术的结果。
This study examined the role of sirtuins in the regenerative potential of articular chondrocytes. Sirtuins (SIRT1-7) play a key role in regulating cartilage homeostasis. By inhibiting pro-inflammatory pathways responsible for cartilage degradation and promoting the expression of key matrix components, sirtuins have the potential to drive a favourable balance between anabolic and catabolic processes critical to regenerative medicine. When subjected to osmolarity and glucose concentrations representative of the in vivo niche, freshly isolated bovine chondrocytes exhibited increases in SIRT1 but not SIRT3 gene expression. Replicating methods adopted for the in vitro monolayer expansion of chondrocytes for cartilage regenerative therapies, we found that SIRT1 gene expression declined during expansion. Manipulation of sirtuin activity during in vitro expansion by supplementation with the SIRT1-specific activator SRT1720, nicotinamide mononucleotide, or the pan-sirtuin inhibitor nicotinamide, significantly influenced cartilage regeneration in subsequent 3D culture. Tissue mass, cellularity and extracellular matrix content were reduced in response to sirtuin inhibition during expansion, whilst sirtuin activation enhanced these measures of cartilage tissue regeneration. Modulation of sirtuin activity during monolayer expansion influenced H3K27me3, a heterochromatin mark with an important role in development and differentiation. Unexpectedly, treatment of primary chondrocytes with sirtuin activators in 3D culture reduced their matrix synthesis. Thus, modulating sirtuin activity during the in vitro monolayer expansion phase may represent a distinct opportunity to enhance the outcome of cartilage regenerative medicine techniques.
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影响因子：
5.6
作者：
Heywood, Hannah K.;Lee, David A.
通讯作者：
Lee, David A.
影响因子：
--
作者：
Gabay, Odile;Sanchez, Christelle;Dvir-Ginzberg, Mona;Gagarina, Viktoria;Zaal, Kristien J.;Song, Yingjie;He, Xiao Hong;McBurney, Michael W.
通讯作者：
McBurney, Michael W.
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
5.6
作者：
Heywood, HK;Bader, DL;Lee, DA
通讯作者：
Lee, DA
影响因子：
4.8
作者：
Hong, Eun-Hee;Yun, Hong Shik;Hwang, Sang-Gu
通讯作者：
Hwang, Sang-Gu