Matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms promote increase and remodeling of the collagen III and V in posterior tibial tendinopathy
Universidad de Murcia. Departamento de Biología Celular e Histología
Doi
Abstract
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 (MMP1) 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