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Vascular endothelial growth factor enhances tendon-bone healing by activating Yes-associated protein for angiogenesis induction and rotator cuff reconstruction in rats.

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.

Authors+Show Affiliations

Sports Medicine Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.Department of Dermatology, Nanjing First Hospital, Nanjing, China.Sports Medicine Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.Sports Medicine Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.Sports Medicine Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.Sports Medicine Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31633245

Citation

Huang, Yao, et al. "Vascular Endothelial Growth Factor Enhances Tendon-bone Healing By Activating Yes-associated Protein for Angiogenesis Induction and Rotator Cuff Reconstruction in Rats." Journal of Cellular Biochemistry, 2019.
Huang Y, Pan M, Shu H, et al. Vascular endothelial growth factor enhances tendon-bone healing by activating Yes-associated protein for angiogenesis induction and rotator cuff reconstruction in rats. J Cell Biochem. 2019.
Huang, Y., Pan, M., Shu, H., He, B., Zhang, F., & Sun, L. (2019). Vascular endothelial growth factor enhances tendon-bone healing by activating Yes-associated protein for angiogenesis induction and rotator cuff reconstruction in rats. Journal of Cellular Biochemistry, doi:10.1002/jcb.29457.
Huang Y, et al. Vascular Endothelial Growth Factor Enhances Tendon-bone Healing By Activating Yes-associated Protein for Angiogenesis Induction and Rotator Cuff Reconstruction in Rats. J Cell Biochem. 2019 Oct 21; PubMed PMID: 31633245.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vascular endothelial growth factor enhances tendon-bone healing by activating Yes-associated protein for angiogenesis induction and rotator cuff reconstruction in rats. AU - Huang,Yao, AU - Pan,Min, AU - Shu,Hao, AU - He,Bing, AU - Zhang,Fucheng, AU - Sun,Luning, Y1 - 2019/10/21/ PY - 2019/03/07/received PY - 2019/10/10/accepted PY - 2019/10/22/entrez KW - VEGF KW - YAP KW - rotator cuff KW - shoulder KW - tendon-bone healing JF - Journal of cellular biochemistry JO - J. Cell. Biochem. N2 - 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. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/31633245/Vascular_endothelial_growth_factor_enhances_tendon-bone_healing_by_activating_Yes-associated_protein_for_angiogenesis_induction_and_rotator_cuff_reconstruction_in_rats L2 - https://doi.org/10.1002/jcb.29457 DB - PRIME DP - Unbound Medicine ER -