Triiodothyronine potentiates angiogenesis-related factor expression through PI3K/AKT signaling pathway in human osteoarthritic osteoblasts

• Main Authors: Li Lei, Pang Yiqun, Linlin Zhang, Meng Li, Zhu Chen, Shiyuan Fang, Yin Zongsheng
• Format: Article
• Language: English
• Published: Mashhad University of Medical Sciences 2020-06-01
• Series: Iranian Journal of Basic Medical Sciences
• Subjects: hif-1α; osteoarthritis; osteoblast; pi3k; thyroid hormone; vegf
• Online Access: http://ijbms.mums.ac.ir/article_15512_61e9a3a79f4c629aee652708a16f2798.pdf

<em><strong>Objective(s):</strong> </em>Previous study has indicated that triiodothyronine (T3) facilitated cartilage degeneration in osteoarthritis (OA). This study aimed to investigate the effects of T3 on angiogenesis-related factor expression in human osteoblasts of OA subchondral bone.<br /><em><strong>Materials and Methods:</strong> </em>The subchondral bone specimens were obtained from OA patients and healthy participants. The expressions of VEGF, HIF-1α, AKT, and phosphorylated AKT was detected by immunohistochemistry, Western blotting, and RT-qPCR in OA. Angiogenesis-related factor expression in OA osteoblasts was measured by treating different concentrations of T3. The hypoxia model and PX-478 (HIF-1α inhibitor) were employed to confirm the regulative role of HIF-1α for VEGF expression. The level of VEGF secretion was examined in osteoblasts supernatant using ELISA.   <br /><em><strong>Results:</strong> </em>Immunohistochemistry showed strong staining of VEGF and HIF-1α in OA subchondral bone. The expression of VEGF, HIF-1α, and p-AKT in OA osteoblasts was higher than that of normal osteoblasts at protein and mRNA levels. The physiological concentration of T3 (10-7 M) in OA osteoblasts up-regulated the expression of VEGF, HIF-1α, and p-AKT after 24 hr and 48 hr culture, while a higher dose of T3 displayed the adverse effects. Additionally, VEGF and p-AKT expression was down-regulated when PX-478 inhibited HIF-1α protein. <br /><em><strong>Conclusion:</strong></em> Our results suggested that local T3 could effectively increase angiogenesis-related factor expression by PI3K/AKT signaling pathway, and HIF-1α regulated the VEGF expression in OA osteoblasts.