Shaliny KrishnanHui Yin NamAmirah ZulkifliPeggy KongCheh Chin TaiAzura MansorTunku Kamarul2025-10-312025-10-312025-1010.1016/j.tice.2025.103018https://dspace-cris.utar.edu.my/handle/123456789/11662Uniaxial cyclic strain induces tenogenic differentiation of mesenchymal stromal cells (MSCs), suggesting its beneficial role in tendon regeneration following injury. However, pro-inflammatory cytokines released during injury is expected to impede repair outcomes but has not been previously considered. A study was thus conducted to determine the effects of interleukin-1-beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) on the tenogenic differentiation potential of cyclic strained MSCs. An in vitro model of MSCs exposed to IL-1 beta (9 ng/ml) and TNF-alpha (6 ng/ml) in unstrained and strained conditions, were developed. The effect of these cytokines on MSCs functional properties including proliferation, viability, anabolic/catabolic protein production and tenogenic differentiation potential of MSCs were quantified. IL-1 beta (9 ng/ml) and TNF-alpha (6 ng/ml) reduced unstrained MSCs viability, proliferation, ECM protein production and tenogenic markers expression whilst increasing matrix metalloproteinase 13 (MMP-13) expression. Uniaxial strain exposure in IL-1 beta-treated MSCs reversed the inhibitory effects of this cytokine on cell proliferation, collagen production and tenogenic markers expression. The significant reduction in tenogenic potential observed in MSCs treated with TNF-alpha was not alleviated by cyclic strain. These data indicate that TNF-alpha and not IL-1 beta is able to inhibit tenogenic effects induced by uniaxial cyclic strain on MSCs.enMesenchymal stromal cellsPro-inflammatory cytokinesUniaxial cyclic strainTenogenic differentiationMECHANICAL STRETCHGENE-EXPRESSIONTENDONPROLIFERATIONMETALLOPROTEINASESTRANSCRIPTIONCOLLAGENBIOLOGYjournal-article