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

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.

Understanding cellular and molecular mechanisms of pathogenesis of diabetic tendinopathy

“…The diabetic patellar tendon had significantly decreased stiffness with a reduced Young’s modulus[ 15 ]. However, Thomas et al [ 35 ] showed that hyperglycemia did not alter mechanics (stiffness and modulus) at either insertion site or mid-substance of the supraspinatus tendon, while some studies showed no significant changes in biomechanical properties between diabetic and nondiabetic tendons[ 12 , 36 ].…”

“…The repair and regenerative capacity of diabetic tendons is compromised during the healing process after injury. Fibroblast proliferation[ 43 , 44 ], vascularity[ 21 , 44 , 45 ], and collagen levels[ 36 , 44 ] were reduced in injured diabetic tendons during healing. Egemen et al [ 43 ] showed that although similar collagen deposition and vessel proliferation were observed in both injured diabetic and nondiabetic tendons during healing, lymphocyte infiltration and osteochondroid metaplasia of some tenocytes were observed in the injured diabetic tendons.…”

Efeitos do extrato de Allium cepa L. na morfologia da mucosa duodenal de ratos diabéticos

“…Os dados glicêmicos dos animais estão representados na Tabela 1. Conforme mostra a tabela os animais permaneceram hiperglicêmicos até o fim do período experimental assim como nos demais estudos com o mesmo modelo experimental (DE OLIVEIRA et al, 2019). O grupo DAC teve a glicemia reduzida significativamente versus o grupo D, mostrando o potencial hipoglicemiante desta planta (LEE et al, 2013).…”

Responses of matrix metalloproteinases to hyperbaric oxygen treatment: changing for good or ill?

“…Disorders affecting the musculoskeletal system have also been shown to be associated with changes in MMPs since tendon, bone, articular cartilage, ligament, and other components are ECM-rich organs 18 . The connective tissue predominating in such structures constitutes mainly of fibrillar collagen (type I, II, and III) as they have load-bearing roles 10,16,24 . Hence, tightly regulated ECM degradation is required from MMPs, especially the collagenases.…”

“…Regulation of MMPs must be notably tight, otherwise either their inhibition or overexpression can easily lead to breakdown of tissue homeostasis 13 . Structural alterations associated with MMP dysregulation manifest as, among others, impaired healing 14 , organ fibrosis, 15 and ECM disorganization 16 . Interestingly, MMPs have been shown to be responsive to HBO 2 , making them a key target for investigation 3,6 .…”