Abstract
Objective and Design:To determine whether fibronectin fragments (Fn-f) upregulate nitric oxide (NO) and inducible NO synthetase (iNOS) levels in explants and whether iNOS inhibitors block Fn-f mediated cartilage damage or promote repair. Material: Bovine cartilage explants were studied.
Treatment:Explants were cultured with Fn-f and involvement of NO pathway investigated.
Methods:Induction of iNOS was tested by RT-PCR. Upregulation of iNOS protein was visualized by Western blotting. Proteoglycan (PG) content of cartilage treated with iNOS inhibitors was tested by dye binding assays of cartilage digests.
Results:Fn-fs elevated NO release in explants and upregulated iNOS protein and mRNA while native Fn had only weak activity. Three different iNOS inhibitors blocked Fn-f mediated PG depletion from explants and facilitated restoration of PG in pre-damaged cartilage.
Conclusions:The Fn-f cartilage damaging pathway involves upregulation of iNOS. Interestingly, iNOS inhibitors not only blocked damage but repaired damaged cartilage. This may be the first report of reparative activities of iNOS inhibitors.
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Received 25 August 2003; returned for revision 7 October 2003; accepted by W. van den Berg 6 April 2004
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Pichika, R., Homandberg, G.A. Fibronectin fragments elevate nitric oxide (NO) and inducible NO synthetase (iNOS) levels in bovine cartilage and iNOS inhibitors block fibronectin fragment mediated damage and promote repair. Inflamm. res. 53, 405–412 (2004). https://doi.org/10.1007/s00011-004-1279-8
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DOI: https://doi.org/10.1007/s00011-004-1279-8