Author(s): GARRIDO, P.M., PAPADOPETRAKI, A., SVENSSON, R.B., MAGNUSSON, S.P., PHILIPPOU, A., BACKMAN, L.B., GIANNOPOULOS, A. , Institution: LOUGHBORUGH UNIVERSITY, Country: UNITED KINGDOM, Abstract-ID: 1248

INTRODUCTION:
Insulin-like Growth Factor-1 (IGF-1) has a regulatory role in tendon healing and IGF-1 injections have been used as a treatment in tendinopathies. Exercise alters systemic responses which can have anabolic or catabolic actions. The purpose of this study was to assess if the baseline levels of IGF-1 or Insulin-like growth factor-binding protein 3, (IGFBP-3) in the serum would affect the bioactivity of exogenously added IGF-1 on tendon constructs regeneration capacity.
METHODS:
Seven healthy females that were physically active but not professional athletes volunteered for this study (age: 30.86 ± 5.05 years, height: 1.66 ± 0.03 m, body weight: 61.93 ± 4.31 kg, body mass index: 22.55 ± 1.42 kg/m2). Participants conducted a cardiopulmonary exercise testing (CPET) protocol, consisting of a maximal incremental protocol on a cycle ergometer with 3-minute stages, aiming to last 8-12 minutes. During the test, gas exchange was monitored continuously, through a breath-by-breath exercise metabolic analyzer. On a separate day, the participants performed one exercise session on a cycle ergometer at 80% of their peak oxygen uptake (VO2peak) and serum was collected before and after the exercise session. Human tendon constructs (N=56) treated with serum from each participant consisting of the following conditions: Pre- (Pre-Ex+IGF-1) and post-exercise serum (Post-Ex+IGF-1) supplemented with IGF-1, pre- (Pre-Ex) and post-exercise (Post-Ex) serum without IGF-1. Enzyme-linked immunosorbent assays were used to evaluate serum levels of IGF-1 and IGFBP-3 and collagen type I in the cultured media. Protein concentration was measured with Bicinchoninic acid assay.
RESULTS:
Free IGF-1 levels in the circulation showed a 30.6% increase as measured in post-exercise serum compared to pre-exercise values. IGFBP-3 remained unaltered after the exercise session. Treatment with IGF-1 had a significant negative effect on collagen type I overall secretion (p=0.03) with a 9.5 % decrease of Pre-Ex+IGF-1 and 28.6% of Post-Ex+IGF-1 compared to Pre-Ex and Post-Ex groups respectively, with no significant correlation with IGF-1 or IGFBP-3 serum levels. Both exercise (p=0,014) and IGF-1 treatment (p<0.0001) altered the total protein concentration. The supplementation of IGF-1 resulted in increased protein synthesis at the pre-exercise (Pre-Ex+IGF-1>Pre-Ex, p=0.06) by 28.2% and the post-exercise (Post-Ex+IGF-1>Post-Ex, p=0.0005) by 31.8% compared to the relative groups before the exercise.
CONCLUSION:
IGF-1 treatment caused a reduction of the secreted collagen type I indicating that more collagen was incorporated into the construct structure. The above process did not correlate with the amount of IGF-1 and IGFBP3 in the serum, suggesting that treatment efficacy depends more on the administrative dose. Post-serum systemic environment enhanced IGF-1 effect on protein synthesis of tendon constructs providing a useful condition that could be considered for designing treatment strategies targeting tendon regeneration.