Matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms promote increase and remodeling of the collagen III and V in posterior tibial tendinopathy
Tulio Diniz-Fernandes1, Alexandre Leme Godoy-Santos1, Maria Cristina Santos2, Pedro Pontin1, Caio Augusto Alves Pereira3, Yuri Justi Jardim3, Ana Paula Pereira Velosa3, Nicola Maffulli4, Walcy Rosolia Teodoro3 and Vera Luiza Capelozzi5
1Department of Orthopedic Surgery, University of São Paulo, São Paulo, 2Department of Genetic, Federal University of Paraná, PR, Curitiba, Paraná, 3Department of Rheumatology, University of São Paulo, São Paulo, Brasil, 4Centre for Sports and Exercise Medicine Barts and The London School of Medicine and Dentistry, London, United Kingdom and 5Department of Pathology, University of São Paulo, São Paulo, Brazil
Offprint requests to: Walcy Rosolia Teodoro, PhD, Discipline of Rheumatology, University of São Paulo, Brazil. e-mail: walcy.teodoro@fm.usp.br or Vera Luiza Capelozzi, MD ,PhD, Associate Professor of Lung Pathology, Department of Pathology, University of São Paulo, Brazil. vera.capelozzi@fm.usp.br
Summary. 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. Histol Histopathol 33, 929-936 (2018)
Key words: Tendinopathy, Genetic, Extracellular matrix, Metalloproteinase, Collagen
DOI: 10.14670/HH-11-982