Effect of photobiomodulation and exercise on early remodeling of the Achilles tendon in streptozotocin-induced diabetic rats

PLoS One. 2019 Feb 4;14(2):e0211643. doi: 10.1371/journal.pone.0211643. eCollection 2019.

Abstract

The aim of this study was to compare the treatment effects of laser photobiomodulation (LPBM) therapy and aerobic exercise on the biomechanical properties, tissue morphology and the expression of tendon matrix molecules during early remodeling of Achilles tendon (AT) injury in diabetic rats. Animals were randomly assigned to five groups: injured non diabetic (I, n = 15), injured diabetic (ID, n = 15), injured diabetic plus LPBM (IDL, n = 16), injured diabetic plus aerobic exercise (IDE, n = 16) and injured diabetic plus aerobic exercise and LPBM (IDEAL, n = 17). Type 1 diabetes was induced via a single intravenous injection of Streptozotocin at a dose of 40 mg/kg. A partial tenotomy was performed in the right AT. LPBM was performed with an indium-gallium-aluminum-phosphide 660 nm 10 mW laser device (spot size 0.04 cm2, power density 250 mW/cm2, irradiation duration 16 s, energy 0.16 J, energy density 4 J/cm2) on alternate days for a total of 9 sessions over 3 weeks (total energy 1.44 J), using a stationary contact technique to a single point over the dorsal aspect of the AT. Moderate aerobic exercise was performed on a motorized treadmill (velocity 9 m/min for 60 minutes). At 3 weeks post-injury, biomechanical analyzes as well as assessment of fibroblast number and orientation were performed. Collagen 1 (Col1) and 3 (Col3) and matrix metalloproteinases (MMPs) -3 and 13 protein distributions were studied by immunohistochemistry; while Col1 and Col3 and MMP-2 and 9 gene expression were assessed by quantitative RT-PCR (qRT-PCR). IDEAL exhibited significant increases in several biomechanical parameters in comparison to the other groups. Moreover, IDEAL presented stronger Col1 immunoreactivity when compared to ID, and weaker Col3 immunoreactivity than IDE. Both IDL and IDEAL demonstrated weaker expression of MMP-3 in comparison to I, while IDL presented no expression of MMP-13 when compared to ID. ID, IDL and IDE showed an increased number of fibroblasts in comparison to I, while IDEAL decreased the number of these cells in comparison to ID and IDE. IDL and IDEAL groups exhibited decreased angular dispersion among the fibroblasts when compared to I. The gene expression results showed that IDE demonstrated a downregulation in Col1 mRNA expression in comparison to I and ID. IDEAL demonstrated upregulation of Col1 mRNA expression when compared to IDL or IDE alone and increased MMP-2 expression when compared to IDL and IDE. MMP-9 expression was upregulated in IDEAL when compared to I, IDL and IDE. Our results suggest a beneficial interaction of combining both treatment strategies i.e., aerobic exercise and LPBM, on the biomechanical properties, tissue morphology and the expression of matrix molecules in diabetic tendons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / metabolism
  • Achilles Tendon / physiopathology*
  • Animals
  • Collagen Type I / metabolism
  • Collagen Type III / metabolism
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / etiology
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Fibroblasts / metabolism
  • Low-Level Light Therapy / methods
  • Male
  • Metalloendopeptidases / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Streptozocin / pharmacology
  • Tendon Injuries / etiology
  • Tendon Injuries / metabolism
  • Tendon Injuries / physiopathology
  • Tendon Injuries / therapy*
  • Up-Regulation / physiology
  • Wound Healing / physiology

Substances

  • Collagen Type I
  • Collagen Type III
  • RNA, Messenger
  • Streptozocin
  • Metalloendopeptidases

Grants and funding

W.H.B.V. received support from the Brazilian National Council for Scientific and Technological (CNPq grant number 480758/2013-1).