Vascular endothelial growth factor enhances tendon‐bone healing by activating Yes‐associated protein for angiogenesis induction and rotator cuff reconstruction in rats. Issue 3 (21st October 2019)

• Record Type: Journal Article
• Authors: Huang, Yao; Pan, Min; Shu, Hao; He, Bing; Zhang, Fucheng; Sun, Luning
• Is Part Of: Journal of cellular biochemistry. Volume 121:Issue 3(2020)
• Page Start: 2343
• Page End: 2353
• Publication Date: 2019-10-21
• Subjects: rotator cuff -- shoulder -- tendon‐bone healing -- VEGF -- YAP; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29457
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Local angiogenesis following rotator cuff reconstruction is crucial for tendon‐bone healing. The current research on the mechanism underlying angiogenesis that promotes tendon‐bone healing is scarce. This study investigates the mechanism underlying vascular endothelial growth factor (VEGF)‐Hippo signaling pathway's involvement in tendon‐bone healing following rotator cuff reconstruction. Verteporfin, the inhibitor of the Yes‐associated protein (YAP), was used to mechanically test and analyze two groups of tensile‐failure loads following rotator cuff reconstruction and to detect collagen and angiogenesis‐related marker expressions in the tendon. The interaction mechanism of the VEGF‐Hippo signaling pathway was assessed using human umbilical vein endothelial cells (HUVECs). The diameter of the supraspinatus tendon reduced following verteporfin treatment. Mechanical tests revealed that verteporfin significantly reduces the tensile‐failure load of the supraspinatus tendon. Verteporfin significantly reduces collagen 1 (Col 1), Col 3, Angiopoietin 2, CD31, Von Willebrand factor, CTGF, and CYR61 expressions. In HUVECs, VEGF activates VEGF receptors and inhibits LATS and YAP phosphorylation. YAP is then transferred to the nucleus to further activate downstream pathways. Therefore, verteporfin can inhibit VEGF‐induced YAP pathway activation by inhibiting YAP activity. Angiogenesis in tendon‐bone healing following rotator cuff reconstruction requires VEGF‐Hippo signaling pathway synergy. Abstract : This study confirms the important role of angiogenesis, which is regulated by the Hippo signaling pathway, in rotator cuff healing. Vascular endothelial growth factor (VEGF)‐VEGF receptor activates Akt and ERK, inhibits Yes‐associated protein phosphorylation in the Hippo signaling pathway, induces angiogenesis, and enhances tendon‐bone healing in rotator cuff reconstruction in rats.