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Published on: August 21, 2021
Doxycycline impairs tendon repair in rats
Björn Pasternak1, Mårten Fellenius, Per Aspenberg
1Division of Orthopaedics, Department of Neuroscience and Locomotion, Faculty of Health Sciences, Linköping University, Sweden. bjopa266@student.liu.se
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.
Insights
Doxycycline, an antibiotic, impairs rat Achilles tendon healing by inhibiting matrix metalloproteinases (MMPs). This study shows doxycycline significantly reduces tendon strength and energy absorption during the crucial healing process.
Area of Science:
- Biomedical Science
- Orthopedic Research
- Pharmacology
Background:
- Doxycycline is known to inhibit matrix metalloproteinases (MMPs), enzymes crucial for extracellular matrix degradation and tissue repair.
- Matrix metalloproteinases play a vital role in connective tissue remodeling and the healing of injuries.
Purpose of the Study:
- To investigate the effect of doxycycline on the healing process of transected rat Achilles tendons.
- To determine if doxycycline negatively influences tendon regeneration and mechanical properties.
Main Methods:
- 60 Sprague Dawley rats underwent transverse Achilles tendon transection.
- Animals were administered doxycycline at 130 mg/kg/day.
- Tendon healing was mechanically evaluated at 5, 8, and 14 days post-surgery.
Main Results:
- Doxycycline treatment significantly decreased the force at failure (p < 0.005) and energy uptake (p < 0.001) in healing tendons.
- Achieved doxycycline serum concentration was 3.4 (SD 1.0) microg/ml, considered clinically relevant.
- Impaired mechanical properties indicate compromised tendon healing.
Conclusions:
- Doxycycline negatively affects tendon healing in rats at clinically relevant serum concentrations.
- The inhibition of matrix metalloproteinases by doxycycline impedes tendon regeneration and reduces mechanical strength.
- Findings suggest caution when using doxycycline in patients with tendon injuries and highlight the role of MMPs in tendon repair.
