4.5 Article

Effects of tamoxifen on tendon homeostasis and healing: Considerations for the use of tamoxifen-inducible mouse models

Journal

JOURNAL OF ORTHOPAEDIC RESEARCH
Volume 39, Issue 7, Pages 1572-1580

Publisher

WILEY
DOI: 10.1002/jor.24767

Keywords

fibrosis; mouse model; tamoxifen; tendon healing; tendon homeostasis

Categories

Funding

  1. National Institute of Arthritis and Musculoskeletal and Skin Diseases [F31 AR074815, F31 AR077398, K01 AR068386, P30 AR069655, R01 AR056696, R01 AR073169]
  2. NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [F31AR077398] Funding Source: NIH RePORTER

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This study investigated the effects of tamoxifen on tendon homeostasis and healing in mice. The results showed that tamoxifen had no effect on tendon healing in male mice, while it significantly decreased Max load in female repairs. Additionally, tamoxifen treatment led to disruptions in tendon homeostasis in female mice compared to corn oil treatment.
The use of tamoxifen-inducible models of Cre recombinase in the tendon field is rapidly expanding, resulting in an enhanced understanding of tendon homeostasis and healing. However, the effects of tamoxifen on the tendon are not well-defined, which is particularly problematic given that tamoxifen can have both profibrotic and antifibrotic effects in a tissue-specific manner. Therefore, in the present study, we examined the effects of tamoxifen on tendon homeostasis and healing in male and female C57Bl/6J mice. Tamoxifen-treated mice were compared to corn oil (vehicle)-treated mice. In the washout treatment regimen, mice were treated with tamoxifen or corn oil for 3 days beginning 1 week prior to undergoing complete transection and surgical repair of the flexor digitorum longus tendon. In the second regimen, mice were treated with tamoxifen or corn oil beginning on the day of surgery, daily through day 2 postsurgery, and every 48 hours thereafter (D0-2q48) until harvest. All repaired tendons and uninjured contralateral control tendons were harvested at day 14 postsurgery. Tamoxifen treatment had no effect on tendon healing in male mice, regardless of the treatment regimen, while Max load was significantly decreased in female repairs in the Tamoxifen washout group, relative to corn oil. In contrast, D0-2q48 corn oil treatment in female mice led to substantial disruptions in tendon homeostasis, relative to washout corn oil treatment. Collectively, these data clearly define the functional effects of tamoxifen and corn oil treatment in the tendon and inform future use of tamoxifen-inducible genetic models.

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