SAT-LB094 The Role of Thyroid Hormone in the Beneficial Effects of Stretching

Abstract

Pain after musculoskeletal injury is a widespread problem significantly affecting quality of life. Stretching is a common therapy that targets connective tissue that can reduce inflammation and collagen production which otherwise could interfere with normal tissue repair [1]. Thyroid hormone (TH) is critical for a diverse range of biological functions, and TH action is controlled at many levels including production, secretion, transport into the cell, TH receptor and cofactor expression, and by tissue- and cell-specific local deiodination that can either activate or inactivate TH. Studies have found T3-treatment significantly attenuated experimental lung injury and further, T3-treatment has been shown to antagonize well known mediators of fibrosis including TGFB-1, leading to less collagen deposition in liver and skin fibrosis [2, 3]. We hypothesized that stretching will increase T3-action in fibroblasts residing in subcutaneous connective tissue, resulting in less fibrosis. Using an in vivo model, C57BL/6J mice were stretched once for 10 minutes by gently lifting at the base of the tail until reaching a 45° angle while allowing the front paws a grasp a horizontal bar. Control animals were either housed individually for 10 minutes to mimic the stressful effects of handling (non-stretched + stress) or remained in their home cage (non-stretched - stress). Lower back subcutaneous connective tissue was collected 24h later to assess gene expression. We found that TH receptor alpha and beta (Thra and Thrb) were both expressed, as well as the TH transporters MCT8, MCT10, Lat1, and Lat2, while expression of thyroid hormone activating and inactivating deiodinases (Dio2 and Dio3 respectively) was negligible. Notably, comparison to the naïve, non-stretched - stress group indicated that the stress of handling alone appeared to change the expression of many genes including Thra and Thrb. Interestingly, comparisons between stretched and non-stretched + stress groups revealed decreased expression of genes involved in collagen synthesis including Col1a1 and CTGF. In conclusion, connective tissue has the necessary components to respond to T3 and one acute session of stretching was sufficient to decrease expression of genes associated with fibrosis although components of the TH action-pathway were not specifically changed.