rhPDGF-BB combined with ADSCs in the treatment of Achilles tendinitis via miR-363/PI3 K/Akt pathway

Mol Cell Biochem. 2018 Jan;438(1-2):175-182. doi: 10.1007/s11010-017-3124-8. Epub 2017 Aug 1.

Abstract

To investigate the mechanism of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and human adipose-derived stem cells (hADSCs) in the treatment of Achilles tendinitis. Biomechanical indices of stiffness, stress, and maximum load-to-failure were detected by biomechanical test. mRNA and protein levels of miR-363, p-PI3K/AKT, tendon-related genes Collagen I, Scleraxis (Scx), and Tenascin C (TNC) were measured by qRT-PCR and western blot. The proliferation of hADSCs was accessed by MTT assay. Biomechanical indices of stiffness, stress, and maximum load-to-failure, and mRNA and protein levels of tendon-related genes could be improved by rhPDGF-BB or hADSCs alone, and could be further improved by rhPDGF-BB + hADSCs. rhPDGF-BB and hADSCs downregulated the expression of miR-363 and upregulated the levels of p-PI3K/Akt, and rhPDGF-BB + hADSCs further strengthened these effects. In addition, rhPDGF-BB promoted the proliferation of hADSCs in vitro and upregulated the expression of tendon-related genes. miR-363 mimic downregulated the levels of p-PI3K/Akt, miR-363 inhibitor upregulated the levels of p-PI3K/Akt, and miR-363 mimic and PI3K/Akt pathway inhibitor LY294002 reversed the positive effect of rhPDGF-BB on the proliferation of hADSCs, which suggested that rhPDGF-BB promoted the proliferation of hADSCs via miR-363/PI3K/Akt pathway. Biomechanical indices and tendon-related genes could be improved by rhPDGF-BB and hADSCs. Moreover, rhPDGF-BB promoted the proliferation of hADSCs via miR-363/PI3K/Akt pathway, indicating that rhPDGF-BB combined with ADSCs could treat Achilles tendinitis via miR-363/PI3K/Akt pathway.

Keywords: Achilles tendinitis; PI3K/Akt pathway; hADSCs; miR-363; rhPDGF-BB.

MeSH terms

  • Achilles Tendon*
  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology
  • Animals
  • Becaplermin
  • Disease Models, Animal
  • Heterografts
  • Humans
  • Proto-Oncogene Proteins c-sis / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation*
  • Stem Cells / metabolism*
  • Stem Cells / pathology
  • Tendinopathy / metabolism
  • Tendinopathy / pathology
  • Tendinopathy / therapy*

Substances

  • Proto-Oncogene Proteins c-sis
  • Becaplermin