RESUMO
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.
Assuntos
Condrócitos , Colágeno , Condrócitos/metabolismo , Colágeno/metabolismo , Dipeptídeos/farmacologia , Dipeptídeos/metabolismo , Diferenciação Celular/fisiologia , Peptídeos/farmacologia , Peptídeos/metabolismo , Células CultivadasRESUMO
Lukianol A (1a) and its six derivatives 1b-1g, in which each hydroxyl groups of 1a was individually modified, were synthesized via the common intermediate 7a, which was obtained by condensation of the styryl carbazate 10 with p-hydroxyphenylpyruvic acid and subsequent [3,3]-sigmatropic rearrangement. The synthesized lukianol derivatives were evaluated for their ability to inhibit human aldose reductase. 4'-O-methyl (1b) and 4'-dehydroxy (1g) derivatives showed the same level of inhibitory activity as 1a (IC50 2.2 µm), indicating that the 4'-OH is irrelevant for the activity. In contrast, methylation of the hydroxyl group at the 4â³'-position (1d) resulted in the loss of activity at a concentration of 10 µm, and masking the hydroxyl group at the 4â³-position (1e) caused a 9-fold decrease in activity compared with that of 1b, suggesting that the 4â³-OH is an essential group, and the 4â³'-OH is required for higher activity.