Donor-dependent regulation of type II and X collagen deposition by early modulation of miR-335-5p and miR-1246 during chondrogenic commitment

• Inhibition of miR-1246 and miR-335-5p enhances chondrogenic and hypertrophic differentiation in human BMSCs, but only in a subset of donors, indicating donor-specific responses. • miR-193a-5p inhibition has minimal effect on early endochondral differentiation, suggesting a limited functional role in this process. • Responder donors show significant upregulation of GDF5 and CCN5 and downregulation of SKIL upon miR-335-5p inhibition, providing potential mechanistic targets. • The findings highlight the need for personalized approaches in fracture healing prediction and therapy, as miRNA effects vary among individuals.