title: New insights in extracellular matrix remodeling and collagen turnover related pathways in cultured human tenocytes after ciprofloxacin administration.
abstract: We characterized the effect of ciprofloxacin (CPX) in cultured human tenocytes by morphological and molecular methods. Collagen type I and III mRNA and protein levels were unaffected, but lysyl hydroxylase 2b mRNA levels progressively decreased after CPX administration. MMP-1 protein levels significantly increased after 20 μg/ml CPX administration but remained unmodified at the higher dose, whilst MMP-2 activity was unchanged. Tissue inhibitor of MMP (TIMP-1) gene expression decreased after CPX treatment, whilst TIMP-2 and transforming growth factor-β1 gene expression, the cytoskeleton arrangement, and cytochrome c expression remained unmodified. Secreted Protein Acidic and Rich in Cysteine mRNA and protein levels remained almost unchanged, whilst N-cadherin mRNA levels resulted significantly down-regulated and connexin 43 gene expression tended to decrease after CPX administration. The CPX-induced decreased ability to cross-link collagen and decreased TIMP-1 levels, possibly leading to higher activity of MMPs in ECM degradation, together with the down-regulation of N-cadherin and connexin 43 are consistent with a reduced ability to maintain tissue homeostasis, possibly making the tendon more susceptible to rupture.
authors.affiliation: Department of Biomedical Sciences for Health, Extracellular Matrix Lab, University of Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Menon
authors.affiliation: Department of Biomedical Sciences for Health, Extracellular Matrix Lab, University of Milan, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Pettinari
authors.affiliation: Department of Biomedical Sciences for Health, Extracellular Matrix Lab, University of Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Martinelli
authors.affiliation: Department of Biosciences, University of Milan, Italy.
authors.forename: Graziano
authors.initials: G
authors.lastname: Colombo
authors.affiliation: Department of Pediatric Orthopaedic Surgery, Clinical Institute Humanitas IRCCS, Rozzano, Milan, Italy ; Department of Medical Biotechnology and Translational Medicine, University of Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Portinaro
authors.affiliation: Department of Biosciences, University of Milan, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Dalle-Donne
authors.affiliation: Shock Wave Unit, Rehabilitation Department, Clinical Institute Humanitas IRCCS, Rozzano, Milan, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: d'Agostino
authors.affiliation: Department of Biomedical Sciences for Health, Extracellular Matrix Lab, University of Milan, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Gagliano
keywords: ciprofloxacin; collagen turnover; extra-cellular matrix remodelling; tendons; tenocytes