Med Sci Sports Exerc. 2017 Apr 11. doi: 10.1249/MSS.0000000000001294. [Epub ahead of print]

Angiopoietin-like 4 Enhances the Proliferation and Migration of Tendon Fibroblasts.

Jamil S¹, Mousavizadeh R, Roshan-Moniri M, Tebbutt SJ, McCormack RG, Duronio V, Scott A.

Abstract

PURPOSE:

Angiopoietin-like 4 (ANGPTL4) is known to play a variety of roles in the response to exercise, and more recently has been shown to enhance the healing of tendon, a fibrous load-bearing tissue required for efficient movement. The objective of the current study was to further explore the mechanisms of ANGPTL4's impact on tendon cells using a gene array approach.

METHODS:

Human tendon fibroblasts were treated with recANGPTL4 and their global transcriptome response analyzed after 4 and 24 hours. We also conducted functional studies using tendon fibroblasts derived from human subjects, cultured in the presence or absence of applied cyclic stretch and/or siRNA for ANGPTL4, and as confirmation we also utilized tendon cells from wild type (ANGPTL4 +/+) or knockout (ANGPTL4-/-) mice.

RESULTS:

The leading functions of ANGPTL4 predicted by the resulting pathway analysis were cell movement and proliferation. The experiments demonstrated that ANGPTL4 significantly enhanced tendon cell proliferation and the cell cycle progression, as well as adhesion and migration.

CONCLUSION:

Taken together, these findings provide novel molecular insights into the impact of ANGPTL4, a multi-functional protein which regulates the physiological response to exercise, on fundamental tendon cell functions.