Tibial dyschondroplasia is highly associated with suppression of tibial angiogenesis through regulating the HIF-1α/VEGF/VEGFR signaling pathway in chickens

• Published in: Scientific reports 2017-08, Vol.7 (1), p.9089-9089, Article 9089
• Main Authors: Huang, Shu-cheng, Rehman, Mujeeb Ur, Lan, Yan-fang, Qiu, Gang, Zhang, Hui, Iqbal, Muhammad Kashif, Luo, Hou-qiang, Mehmood, Khalid, Zhang, Li-hong, Li, Jia-kui
• Format: Article
• Language: English
• Subjects: 38/39; 38/77; 631/136/16/1993; 631/136/819; 631/443/811; 631/601/1737; 692/4017; 82/1; 82/80; Altitude; Angiogenesis; Cartilage; Chickens; Down-regulation; High-altitude environments; Humanities and Social Sciences; Hypoxia; Hypoxia-inducible factors; Interleukin 8; multidisciplinary; Poultry; Science; Science (multidisciplinary); Signal transduction; Thiram; Vascular endothelial growth factor; Vascular endothelial growth factor receptors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-09664-6

Tibial dyschondroplasia (TD) is an intractable poultry problem that is characterized by the appearance of non-vascularized and non-mineralized cartilage masses in tibial growth plates (TGPs). However, the role of angiogenesis inhibition in the occurrence of TD remains unknown. In this study, we found that, compared to low-altitude Arbor Acres chickens (AACs), high-altitude Tibetan chickens showed higher tibial vascular distributions that were accompanied by up-regulation of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA) and VEGF receptors. These observations provide insights into hypoxia-induced angiogenesis, which may be related to the absence of TD in high-altitude native Tibetan chickens. Importantly, hypoxia experiments also showed that during hypoxia, tibial angiogenesis was enhanced, which was due to pro-angiogenic factor up-regulation (including VEGFA, VEGFR1, VEGFR2, and IL-8), in AACs. Moreover, we observed that thiram-induced TD could strongly inhibit tibial angiogenesis in the hypertrophic zone through coordinated down-regulation of HIF-1α and pro-angiogenic factors, leading to a disruption in the blood supply to the TGP. Taken together, these findings reveal that the occurrence of TD is highly associated with inhibition of tibial angiogenesis through down-regulated expression of HIF-1α, VEGFA and VEGF receptors, which results in suppression of TGP development.