TY - JOUR
T1 - Angiopoietin-like 4 promotes angiogenesis in the tendon and is increased in cyclically loaded tendon fibroblasts
AU - Mousavizadeh, Rouhollah
AU - Scott, Alex
AU - Lu, Alex
AU - Ardekani, Gholamreza S.
AU - Behzad, Hayedeh
AU - Lundgreen, Kirsten
AU - Ghaffari, Mazyar
AU - Mccormack, Robert G.
AU - Duronio, Vincent
N1 - Publisher Copyright:
© 2016 The Physiological Society.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - The mechanisms that regulate angiogenic activity in injured or mechanically loaded tendons are poorly understood. The present study examined the potential role of angiopoietin-like 4 (ANGPTL4) in the angiogenic response of tendons subjected to repetitive mechanical loading or injury. Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via transforming growth factor-β (TGF-β) and hypoxia-inducible factor 1α (HIF-1α) signalling, and the released ANGPTL4 was pro-angiogenic. Angiogenic activity was increased following ANGPTL4 injection into mouse patellar tendons, whereas the patellar tendons of ANGPTL4 knockout mice displayed reduced angiogenesis following injury. In human rotator cuff tendons, the expression of ANGPTL4 was correlated with the density of tendon endothelial cells. To our knowledge, this is the first study characterizing a role of ANGPTL4 in the tendon. ANGPTL4 may assist in the regulation of vascularity in the injured or mechanically loaded tendon. TGF-β and HIF-1α comprise two signalling pathways that modulate the expression of ANGPTL4 by mechanically stimulated tendon fibroblasts and, in the future, these could be manipulated to influence tendon healing or adaptation.
AB - The mechanisms that regulate angiogenic activity in injured or mechanically loaded tendons are poorly understood. The present study examined the potential role of angiopoietin-like 4 (ANGPTL4) in the angiogenic response of tendons subjected to repetitive mechanical loading or injury. Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via transforming growth factor-β (TGF-β) and hypoxia-inducible factor 1α (HIF-1α) signalling, and the released ANGPTL4 was pro-angiogenic. Angiogenic activity was increased following ANGPTL4 injection into mouse patellar tendons, whereas the patellar tendons of ANGPTL4 knockout mice displayed reduced angiogenesis following injury. In human rotator cuff tendons, the expression of ANGPTL4 was correlated with the density of tendon endothelial cells. To our knowledge, this is the first study characterizing a role of ANGPTL4 in the tendon. ANGPTL4 may assist in the regulation of vascularity in the injured or mechanically loaded tendon. TGF-β and HIF-1α comprise two signalling pathways that modulate the expression of ANGPTL4 by mechanically stimulated tendon fibroblasts and, in the future, these could be manipulated to influence tendon healing or adaptation.
UR - http://www.scopus.com/inward/record.url?scp=84955070409&partnerID=8YFLogxK
U2 - 10.1113/JP271752
DO - 10.1113/JP271752
M3 - Article
C2 - 26670924
AN - SCOPUS:84955070409
SN - 0022-3751
VL - 594
SP - 2971
EP - 2983
JO - Journal of Physiology
JF - Journal of Physiology
IS - 11
ER -