Li Lei - Department of Orthopaedics,the First Affiliated Hospital of University of Science and Technology of China, #۱۷ Lujiang Road, Hefei, Anhui, China|Department of Orthopaedics, the First Affiliated Hospital of Anhui Medical University, #۲۶۹ Jixi
Pang Yiqun - Department of Radiology, the First Affiliated Hospital of University of Science and Technology of China, #۱۷ Lujiang Road, Hefei, Anhui, China
Linlin Zhang - Department of Orthopaedics,The First Affiliated Hospital of University of Science and Technology of China, #۱۷ Lujiang Road, Hefei, Anhui, China
Meng Li - Department of Orthopaedics,The First Affiliated Hospital of University of Science and Technology of China, #۱۷ Lujiang Road, Hefei, Anhui, China

Objective(s): 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.Materials and Methods: 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.   Results: 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. Conclusion: 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.

HIF-1α, Osteoarthritis, Osteoblast, PI3K, Thyroid hormone, VEGF