Regulatory T Cells Modulate Bone Marrow Stromal Cell Osteogenesis by Activating ROCK-Myosin Axis and Cell Contractility

The study investigates the role of regulatory T cells (Treg) in bone regeneration by examining their direct impact on bone marrow-derived mesenchymal stromal cells (BMSC) osteogenesis. It was found that direct co-culture of human BMSC with Treg led to enhanced osteogenic gene expression, alkaline phosphatase activity, and matrix mineralization compared to indirect co-culture. This interaction is mediated through the ROCK-myosin signaling pathway, which is crucial for cell contractility. Proteomic analysis showed an increase in cytoskeletal and osteogenic regulators in BMSC after direct Treg co-culture. Inhibiting cell contractility reduced osteogenesis, but Treg co-culture helped restore cytoskeletal integrity and differentiation. These results suggest that Treg cells are direct modulators of BMSC mechanobiology and osteogenesis, offering potential therapeutic applications in bone regeneration.