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Muscles Ligaments Tendons J. 2013 Aug 11;3(3):122-31. eCollection 2013 Jul.

New insights in extracellular matrix remodeling and collagen turnover related pathways in cultured human tenocytes after ciprofloxacin administration.

Author information

1
Department of Biomedical Sciences for Health, Extracellular Matrix Lab, University of Milan, Italy.
2
Department of Biosciences, University of Milan, Italy.
3
Department of Pediatric Orthopaedic Surgery, Clinical Institute Humanitas IRCCS, Rozzano, Milan, Italy ; Department of Medical Biotechnology and Translational Medicine, University of Milan, Italy.
4
Shock Wave Unit, Rehabilitation Department, Clinical Institute Humanitas IRCCS, Rozzano, Milan, Italy.

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.

KEYWORDS:

ciprofloxacin; collagen turnover; extra-cellular matrix remodelling; tendons; tenocytes

PMID:
24367771
PMCID:
PMC3838320

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