Abstract
Mechanical loading constantly acts on tendons, and a better understanding of its effects on the tendons is essential to gain more insights into tendon patho-physiology. This study aims to investigate tendon mechanobiological responses through the use of mouse treadmill running as an in vivo model and mechanical stretching of tendon cells as an in vitro model. In the in vivo study, mice underwent moderate treadmill running (MTR) and intensive treadmill running (ITR) regimens. Treadmill running elevated the expression of mechanical growth factors (MGF) and enhanced the proliferative potential of tendon stem cells (TSCs) in both patellar and Achilles tendons. In both tendons, MTR upregulated tenocyte-related genes: collagen type I (Coll. I ∼10 fold) and tenomodulin (∼3–4 fold), but did not affect non-tenocyte-related genes: LPL (adipocyte), Sox9 (chondrocyte), Runx2 and Osterix (both osteocyte). However, ITR upregulated both tenocyte (Coll. I ∼7–11 fold; tenomodulin ∼4–5 fold) and non-tenocyte-related genes (∼3–8 fold). In the in vitro study, TSCs and tenocytes were stretched to 4% and 8% using a custom made mechanical loading system. Low mechanical stretching (4%) of TSCs from both patellar and Achilles tendons increased the expression of only the tenocyte-related genes (Coll. I ∼5–6 fold; tenomodulin ∼6–13 fold), but high mechanical stretching (8%) increased the expression of both tenocyte (Coll. I ∼28–50 fold; tenomodulin ∼14–48 fold) and non-tenocyte-related genes (2–5-fold). However, in tenocytes, non-tenocyte related gene expression was not altered by the application of either low or high mechanical stretching. These findings indicate that appropriate mechanical loading could be beneficial to tendons because of their potential to induce anabolic changes in tendon cells. However, while excessive mechanical loading caused anabolic changes in tendons, it also induced differentiation of TSCs into non-tenocytes, which may lead to the development of degenerative tendinopathy frequently seen in clinical settings.
Highlights
Mechanical loading in the form of exercise produces multiple health benefits for the musculoskeletal system [1]
Similar results were found in Achilles tendons with a significant increase in intensive treadmill running (ITR) over moderate treadmill running (MTR) (Figure 2B; p,6.8E-05)
mechano-growth factor (MGF) expression in the MTR group was comparable with a 5-fold increase over control while MGF expression in the patellar tendons in ITR group was much higher than that in Achilles tendons
Summary
Mechanical loading in the form of exercise produces multiple health benefits for the musculoskeletal system [1]. Tendons, along with muscles and bones, are strengthened by exercise, as indicated by increases in cross-sectional area [2], tendon stiffness [3], and tensile strength [4,5] This tendon strengthening occurs because exercise leads to anabolic responses of tendons such as increase in the formation of type I collagen in peritendinous tissue, as shown by microdialysis measurements [6,7]. One indication of this active tendon response to mechanical loading is the high expression of the anabolic growth hormone gene, IGF-1 [8,9]. How various mechanical loading conditions, such as treadmill running, affects MGF gene expression in tendons remains undefined
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