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

Abstract

Tibetan chickens (TBCs) living in high-altitude hypoxic environment, are characterized by delayed growth and small size as compared to low-altitude broiler chickens. Increasing evidences signify the beneficial effect of oxygen (O2) supplementation in animal's body for regulating their body growth and organ development. However, it is still unclear that whether O2 supplementation has an ameliorative and protective role in TBCs living at high altitude. In this study, we first found that O2 supplementation not only increased the survival rate but also promoted the growth of TBCs associated with bone development. Importantly, we observed that the increase of vascular distribution in the tibial hypertrophic zone could contribute to promote growth and development of the tibia, which is highly correlated with the up-regulated expression level of vascular endothelial growth factor (VEGF)-A and VEGF receptor-1 (VEGFR1). Additionally, hypoxia inducible factor (HIF)-1ɑ also has a stimulative elevation by O2 supplementation. These results were confirmed by histology, immunohistochemistry, qRT-PCR and Western blotting techniques. Altogether, these findings demonstrated that the up-regulation of VEGFA and its receptors are accompanied by proangiogeneic factor (HIF-1α) expression, which were required for angiogenesis to meliorate tibia development of TBCs in hypoxia-induced bone suppression that occurred during O2 supplementation. Thus, O2 supplementation may serve as a good applicant for promoting and meliorating bone development in juvenile high-altitude animals.

Evaluation of the cargo contents and potential role of extracellular vesicles in osteoporosis

“…differences in EVs concentrations (Male, p = 0.02; Female, p = 0.03, Figure 2B) comparing to nonosteoporotic and osteoporotic males. We further confirm the results using a mouse model of osteoporosis [14], mice were divided into 3 groups: AC, HU, and US. Results shown that the number of extracellular vesicles in HU mice was higher than AC (both p = 0.015, Figure 2C).…”

Effects of thiram exposure on liver metabolism of chickens

“…Heme is also an important component of hemoglobin, which plays a key role in the transport of oxygen. Oxygen has been demonstrated to play key roles in blood vessel development and bone formation (59). Previous studies indicated that the chickens exposed to thiram showed weight loss, accompanied by angiogenesis disorder and tibial dyschondroplasia (60,61).…”