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Magnetotherapy has been receiving increased attention as an attractive strategy for modulating cell physiology directly at the site of injury, thereby providing the medical community with a safe and non-invasive therapy. Yet, how magnetic field influences tendon cells both at the cellular and molecular levels remains unclear. Thus, the influence of a low-frequency static magnetic field (2 Hz, 350 mT) on human tendon-derived cells was studied using different exposure times (4 and 8 h; short-term studies) and different regimens of exposure to an 8h-period of magnetic stimulation (continuous, every 24 h or every 48 h; long-term studies). Herein, 8 h stimulation in short-term studies significantly upregulated the expression of tendon-associated genes  SCX , C OL1A1 ,  TNC  and  DCN  ( p  < 0.05) and altered intracellular Ca 2+  levels ( p  < 0.05). Additionally, every 24 h regimen of stimulation significantly upregulated  COL1A1 ,  COL3A1  and  TNC  at day 14 in comparison to control (p < 0.05), whereas continuous exposure differentially regulated the release of the immunomodulatory cytokines IL-1β and IL-10 (p < 0.001) but only at day 7 in comparison to controls. Altogether, these results provide new insights on how low-frequency static magnetic field fine-tune the behaviour of tendon cells according to the magnetic settings used, which we foresee to represent an interesting candidate to guide tendon regeneration.

Uncovering the effect of low-frequency static magnetic field on tendon-derived cells: from mechanosensing to tenogenesis