The effects of lactate and acid on articular chondrocytes function: Implications for polymeric cartilage scaffold design
The effects of lactate and acid on articular chondrocytes function: Implications for polymeric cartilage scaffold design
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乳酸和酸对关节软骨细胞功能的影响：对聚合物软骨支架设计的影响
DOI：
10.1016/j.actbio.2016.06.029
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发表时间：
2016
影响因子：
9.7
通讯作者：
Ouyang Hongwei
中科院分区：
文献类型：
--
作者：
Zhang Xiaolei;Wu Yan;Pan Zongyou;Sun Heng;Wang Junjuan;Yu Dongsheng;Zhu Shouan;Dai Jun;Chen Yishan;Tian Naifeng;Heng Boon Chin;Coen Noelle D.;Xu Huazi;Ouyang Hongwei
聚乳酸-羟基乙酸共聚物（PLGA）和聚乳酸（PLLA）是一类可生物降解的高分子材料，广泛应用于软骨组织工程的支架材料。它们的酸降解产物已被广泛认为对细胞功能有害。然而，乳酸盐而不是乳酸对软骨细胞的生物学效应从未被研究过。这是本研究的主要重点。测量PLGA和PLLA降解介质的乳酸盐的量和pH值（酸）。PLGA和PLLA降解培养基，以及不同的乳酸浓度和暴露时间对软骨细胞增殖和软骨特异性基质合成的影响，通过各种技术，包括全球基因表达谱和基因敲除实验进行了研究。结果表明，PLGA和PLLA降解培养基差异调节软骨细胞增殖和基质合成。乳酸引起的酸性pH抑制软骨细胞增殖和基质合成。乳酸对软骨细胞基质合成的影响具有时间和剂量依赖性。乳酸浓度为100 mM和曝光时间为8小时显着增强基质合成。乳酸盐还可以抑制骨关节炎软骨细胞中软骨基质降解基因的表达，如主要的聚集蛋白聚糖酶ADAMTS 5，同时促进基质合成。乳酸的脉冲添加显示在促进COL 2A 1表达方面更有效。全球基因表达数据和基因敲除实验表明，乳酸通过上调HIF 1A促进基质合成。乳酸对软骨细胞的这些不同的生物学效应将对未来的聚合物软骨scaffolds.Statement的意义乳酸是一种广泛使用的聚合物合成，特别是PLGA和PLLA基板的设计产生影响。虽然已经对这些聚合物进行了物理和生物改性，使其成为更好的软骨支架，但很少关注乳酸（这些聚合物的主要降解产物）对软骨细胞的生物学效应。我们的发现说明了不同的生物功能的乳酸和酸对软骨细胞基质的合成。这些结果可以促进未来的乳酸聚合物基软骨支架的设计
Poly (lactic-co-glycolic acid) (PLGA) and poly-l-lactate acid (PLLA) are biodegradable polymers widely utilized as scaffold materials for cartilage tissue engineering. Their acid degradation products have been widely recognized as being detrimental to cell function. However, the biological effects of lactate, rather than lactic acid, on chondrocytes have never been investigated. This is the major focus of this study. The amounts of lactate and the pH value (acid) of the PLGA and PLLA degradation medium were measured. The effects of PLGA and PLLA degradation medium, as well as different lactate concentrations and timing of exposure on chondrocytes proliferation and cartilage-specific matrix synthesis were investigated by various techniques including global gene expression profiling and gene knockdown experiments. It was shown that PLGA and PLLA degradation medium differentially regulated chondrocyte proliferation and matrix synthesis. Acidic pH caused by lactate inhibited chondrocyte proliferation and matrix synthesis. The effect of lactate on chondrocyte matrix synthesis was both time and dose dependent. A lactate concentration of 100 mM and exposure duration of 8 h significantly enhanced matrix synthesis. Lactate could also inhibit expression of cartilage matrix degradation genes in osteoarthritic chondrocytes, such as the major aggrecanase ADAMTS5, whilst promoting matrix synthesis simultaneously. Pulsed addition of lactate was shown to be more efficient in promoting COL2A1 expression. Global gene expression data and gene knock down experiments demonstrated that lactate promote matrix synthesis through up-regulation of HIF1A. These observed differential biological effects of lactate on chondrocytes would have implications for the future design of polymeric cartilage scaffolds.Statement of SignificanceLactic acid is a widely used substrate for polymers synthesis, PLGA and PLLA in particular. Although physical and biological modifications have been made on these polymers to make them be better cartilage scaffolds, little concern has been given on the biological effect of lactic acid, the main degradation product of these polymers, on chondrocytes. Our finding illustrates the differential biological function of lactate and acid on chondrocytes matrix synthesis. These results can facilitate future design of lactate polymers-based cartilage scaffolds