title: Doxycycline impairs tendon repair in rats.
abstract: Doxycycline exhibits various effects apart from its antimicrobial activity, such as inhibition of matrix metalloproteinases (MMPs). MMPs, mainly collagenases and gelatinases, are capable of degrading virtually all constituents of the extracellular matrix and are critical to connective tissue remodelling and healing. We therefore hypothesised that doxycycline would negatively influence the rat tendon healing process and impede tendon regeneration. The Achilles tendon of 60 Sprague Dawley rats was transected transversely. The animals were treated with doxycycline, 130 mg/kg body weight/day. The healing tendons were evaluated mechanically at 5, 8 and 14 days. Doxycycline significantly decreased force at failure (p < 0.005) and energy uptake (p < 0.001). Doxycycline serum concentration was 3.4 (SD 1.0) microg/ml. In conclusion, tendon healing can be affected by doxycycline at clinically relevant serum concentrations. This observation might be of relevance to further studies exploring effects of MMP-inhibitors on tendon tissue.
authors.affiliation: Division of Orthopaedics, Department of Neuroscience and Locomotion, Faculty of Health Sciences, Linköping University, Sweden. bjopa266@student.liu.se
authors.forename: Björn
authors.initials: B
authors.lastname: Pasternak
authors.forename: Mårten
authors.initials: M
authors.lastname: Fellenius
authors.forename: Per
authors.initials: P
authors.lastname: Aspenberg
mesh_terms: D000125:Achilles Tendon / Q000293:injuries*; D000818:Animals; D004318:Doxycycline / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D005260:Female; D061965:Matrix Metalloproteinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D004318:Doxycycline