Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado-shi 350-0295, Saitama, Japan.
Molecules. 2023 Jun 9;28(12):4664. doi: 10.3390/molecules28124664.
Chondrocytes are surrounded by a lower oxygen environment than other well-vascularized tissues with higher oxygenation levels. Prolyl-hydroxyproline (Pro-Hyp), one of the final collagen-derived peptides, has been previously reported to be involved in the early stages of chondrocyte differentiation. However, whether Pro-Hyp can alter chondrocyte differentiation under physiological hypoxic conditions is still unclear. This study aimed to investigate whether Pro-Hyp affects the differentiation of ATDC5 chondrogenic cells under hypoxic conditions. The addition of Pro-Hyp resulted in an approximately 18-fold increase in the glycosaminoglycan staining area compared to the control group under hypoxic conditions. Moreover, Pro-Hyp treatment significantly upregulated the expression of SOX9, Col2a1, Aggrecan, and MMP13 in chondrocytes cultured under hypoxic conditions. These results demonstrate that Pro-Hyp strongly promotes the early differentiation of chondrocytes under physiological hypoxic conditions. Therefore, Pro-Hyp, a bioactive peptide produced during collagen metabolism, may function as a remodeling factor or extracellular matrix remodeling signal that regulates chondrocyte differentiation in hypoxic cartilage.
软骨细胞周围的氧气环境比其他血管丰富、氧合水平更高的组织要低。脯氨酰-羟脯氨酸（Pro-Hyp）是一种最终的胶原蛋白衍生肽，先前已被报道参与软骨细胞分化的早期阶段。然而，Pro-Hyp 是否能在生理缺氧条件下改变软骨细胞的分化尚不清楚。本研究旨在探讨 Pro-Hyp 是否会影响 ATDC5 软骨细胞在缺氧条件下的分化。与缺氧条件下的对照组相比，添加 Pro-Hyp 可使糖胺聚糖染色面积增加约 18 倍。此外，Pro-Hyp 处理可显著上调缺氧培养软骨细胞中 Sox9、Col2a1、Aggrecan 和 MMP13 的表达。这些结果表明，Pro-Hyp 可强烈促进生理缺氧条件下软骨细胞的早期分化。因此，Pro-Hyp 作为胶原蛋白代谢过程中产生的一种生物活性肽，可能作为一种重塑因子或细胞外基质重塑信号，调节缺氧软骨中的软骨细胞分化。
