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bioRxiv · 10.1101/2020.11.09.374009

Moderate and intensive mechanical loading differentially modulate the phenotype of tendon stem/progenitor cells in vivo

Zhang, J.·Nie, D.·Williamson, K.·McDowell, A.·Hogan, M.·Wang, J. H.-C.
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Abstract

To examine the differential mechanobiological responses of specific resident tendon cells, we developed an in vivo model of whole-body irradiation followed by injection of either tendon stem/progenitor cells (TSCs) expressing green fluorescent protein (GFP-TSCs) or mature tenocytes expressing GFP (GFP-TNCs) into the patellar tendons of wild type C57 mice. Injected mice were subjected to moderate treadmill running (MTR) and intensive treadmill running (ITR). In MTR mice, both GFP-TSC and GFP-TNC injected tendons maintained normal cell morphology with elevated expression of tendon related markers collagen I and tenomodulin. In ITR mice injected with GFP-TNCs, cells also maintained an elongated shape similar to the shape found in normal/untreated control mice, as well as elevated expression of tendon related markers. However, ITR mice injected with GFP-TSCs showed typical tendinopathic changes, such as cell morphology transitioning to a round shape, elevated chondrogenic differentiation, and increased gene expression of non-tenocyte related genes LPL, Runx-2, and SOX-9. Increased gene expression data was supported by immunostaining showing elevated expression of SOX-9, Runx-2, and PPAR{gamma}. This study provides evidence that while MTR maintains tendon homeostasis by promoting the differentiation of TSCs into tenocytes, ITR may cause the development of tendinopathy by inducing non-tenocyte differentiation of TSCs, thus leading to the presence of non-tendinous tissues in tendon.

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Zhang, J., Nie, D., Williamson, K., McDowell, A., Hogan, M., Wang, J. H.-C.. 2020-11-09. Moderate and intensive mechanical loading differentially modulate the phenotype of tendon stem/progenitor cells in vivo. https://doi.org/10.1101/2020.11.09.374009

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