Mechanical stimulation of human tendon stem/progenitor cells results in upregulation of matrix proteins, integrins and MMPs, and activation of p38 and ERK1/2 kinases.

Background Tendons are dense connective tissues subjected
periodically to mechanical stress upon which complex responsive
mechanisms are activated. These mechanisms affect not only the
development of these tissues but also their healing. Despite of the
acknowledged importance of the mechanical stress for tendon
function and repair, the mechanotransduction mechanisms in tendon
cells are still unclear and the elucidation of these mechanisms is
a key goal in tendon research. Tendon stem/progenitor cells (TSPC)
possess common adult stem cell characteristics, and are suggested
to actively participate in tendon development, tissue homeostasis
as well as repair. This makes them an important cell population for
tendon repair, and also an interesting research target for various
open questions in tendon cell biology. Therefore, in our study we
focused on TSPC, subjected them to five different mechanical
protocols, and investigated the gene expression changes by using
semi-quantitative, quantitative PCR and western blotting
technologies. Results Among the 25 different genes analyzed, we can
convincingly report that the tendon-related genes - fibromodulin,
lumican and versican, the collagen I-binding integrins - α1, α2 and
α11, the matrix metalloproteinases - MMP9, 13 and 14 were strongly
upregulated in TSPC after 3 days of mechanical stimulation with 8%
amplitude. Molecular signaling analyses of five key integrin
downstream kinases suggested that mechanical stimuli are mediated
through ERK1/2 and p38, which were significantly activated in 8%
biaxial-loaded TSPC. Conclusions Our results demonstrate the
positive effect of 8% mechanical loading on the gene expression of
matrix proteins, integrins and matrix metalloproteinases, and
activation of integrin downstream kinases p38 and ERK1/2 in TSPC.
Taken together, our study contributes to better understanding of
mechanotransduction mechanisms in TPSC, which in long term, after
further translational research between tendon cell biology and
orthopedics, can be beneficial to the management of tendon repair.