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

Abstract

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.

Isoliquiritigenin blunts osteoarthritis by inhibition of bone resorption and angiogenesis in subchondral bone

“…In order to investigate the potential mechanism, we further performed an immunohistochemistry assay on VEGFR2 and MMP-2. VEGF has been identified as the most important pro-angiogenic factor 48 , 49 . After binding with VEGF receptors on the surface of endothelial cell, which sequentially promote endothelial cells recruitment and proliferation 50 , 51 .…”

Healing of Growth Plate Cartilage by Hypoxia Inducible Factor-1α Inhibitor Apigenin on Thiram Induced Tibial Dyschondroplasia

“…This study examined the treatment of TD by natural HIF-1α inhibitor apigenin and the protective effect of this medicine as antioxidant in liver oxidative stress of thiram induced TD birds. HIF-1α is essential for growth and survival of growth plate chondrocytes, while chondrocytes lacking functional HIF-1α have massive cell death in the growth plate which leads to the bone narrow and exhibit less vascularization (Zhang et al, 2012;Yin et al, 2016;Huang et al, 2017b). Previous reports proposed that major regulation of hypoxic responses in chondrogenesis is controlled by HIF-1α (Schipani, 2005).…”

Oxygen Supplementation Ameliorates Tibial Development via Stimulating Vascularization in Tibetan Chickens at High Altitudes

“…In addition, the area of blood vessel and number of blood vessels in the hypertrophic zone adjacent to the tibial growth plate (3 chicks/group, three different microscopic fields/chick) were counted with two isolated groups using Image-Pro® Plus 6.0. 29 , 30 .…”