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Triiodothyronine potentiates angiogenesis-related factor expression through PI3K/AKT signaling pathway in human osteoarthritic osteoblasts
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 subchon...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mashhad University of Medical Sciences
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351449/ https://www.ncbi.nlm.nih.gov/pubmed/32695299 http://dx.doi.org/10.22038/ijbms.2020.43634.10252 |
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author | Li, Lei Pang, Yiqun Zhang, Linlin Li, Meng Zhu, Chen Fang, Shiyuan Yin, Zongsheng |
author_facet | Li, Lei Pang, Yiqun Zhang, Linlin Li, Meng Zhu, Chen Fang, Shiyuan Yin, Zongsheng |
author_sort | Li, Lei |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7351449 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Mashhad University of Medical Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-73514492020-07-20 Triiodothyronine potentiates angiogenesis-related factor expression through PI3K/AKT signaling pathway in human osteoarthritic osteoblasts Li, Lei Pang, Yiqun Zhang, Linlin Li, Meng Zhu, Chen Fang, Shiyuan Yin, Zongsheng Iran J Basic Med Sci Original Article 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. Mashhad University of Medical Sciences 2020-06 /pmc/articles/PMC7351449/ /pubmed/32695299 http://dx.doi.org/10.22038/ijbms.2020.43634.10252 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Li, Lei Pang, Yiqun Zhang, Linlin Li, Meng Zhu, Chen Fang, Shiyuan Yin, Zongsheng Triiodothyronine potentiates angiogenesis-related factor expression through PI3K/AKT signaling pathway in human osteoarthritic osteoblasts |
title | Triiodothyronine potentiates angiogenesis-related factor expression through PI3K/AKT signaling pathway in human osteoarthritic osteoblasts |
title_full | Triiodothyronine potentiates angiogenesis-related factor expression through PI3K/AKT signaling pathway in human osteoarthritic osteoblasts |
title_fullStr | Triiodothyronine potentiates angiogenesis-related factor expression through PI3K/AKT signaling pathway in human osteoarthritic osteoblasts |
title_full_unstemmed | Triiodothyronine potentiates angiogenesis-related factor expression through PI3K/AKT signaling pathway in human osteoarthritic osteoblasts |
title_short | Triiodothyronine potentiates angiogenesis-related factor expression through PI3K/AKT signaling pathway in human osteoarthritic osteoblasts |
title_sort | triiodothyronine potentiates angiogenesis-related factor expression through pi3k/akt signaling pathway in human osteoarthritic osteoblasts |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351449/ https://www.ncbi.nlm.nih.gov/pubmed/32695299 http://dx.doi.org/10.22038/ijbms.2020.43634.10252 |
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