Matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms promote increase and remodeling of the collagen III and V in posterior tibial tendinopathy

Histol Histopathol. 2018 Sep;33(9):929-936. doi: 10.14670/HH-11-982. Epub 2018 Mar 13.


Posterior tibial tendinopathy (PTT) can lead to acquired flatfoot in adults. Many patients develop PTT without any identifiable risk factors. Molecular changes in extracellular matrix (ECM) and matrix metalloproteinase (MMP) polymorphism may influence the risk of developing PTT. We aim to investigate the association between matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms with changes in collagen I, III and V in PTT. A case-control study with 22 patients and 5 controls was performed. The MMP-1 (2G/2G) and MMP-8 (T/T) genotypes were determined by PCR-restriction fragment length polymorphism. Tendon specimens were evaluated by a histologic semiquantitative score, immunofluorescence and histomorphometry for collagen I, III and V. Tendon specimens from PTT demonstrated marked distortion of the architecture with necrosis, large basophilic areas with disruption of the normal linear orientation of collagen bundles, infiltration of inflammatory cells, dystrophic calcification and ossification. Under immunofluorescence, PTT tendon specimens showed weak green fluorescence and diffuse distribution of collagen I fibers, but strong fluorescence of collagen III and V. The collagen I fibers were significantly decreased whereas an increase of collagen III and V were found in PTT compared to control groups. In addition, PTT group presented a significant association with MMP-1 and MMP-8 gene polymorphisms. Patients with PTT matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms presented an increase of the collagen III and V ratio, suggesting that the higher proportion in degenerated tendons could contribute to a decrease in the mechanical resistance of the tissue. Still, functional and association studies are needed to elucidate evident roles of MMPs in PTT.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Collagen Type III / metabolism*
  • Collagen Type V / metabolism*
  • Extracellular Matrix / metabolism
  • Female
  • Genotype
  • Humans
  • Inflammation
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 8 / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Tendinopathy / metabolism*
  • Tendons / pathology
  • Tibia / pathology


  • Collagen Type III
  • Collagen Type V
  • MMP8 protein, human
  • Matrix Metalloproteinase 8
  • MMP1 protein, human
  • Matrix Metalloproteinase 1