biostudies-literatureKerr BANHLBI NIH HHSNational Heart, Lung, and Blood InstituteNational Cancer InstituteNCI NIH HHS112456https://www.ebi.ac.uk/biostudies/studies/S-EPMC7874523biostudies-literatureUnknown399(2)Identifying patient mutations driving skeletal development disorders has driven our understanding of bone development. Integrin adhesion deficiency disease is caused by a Kindlin-3 (fermitin family member 3) mutation, and its inactivation results in bleeding disorders and osteopenia. In this study, we uncover a role for Kindlin-3 in the differentiation of bone marrow mesenchymal stem cells (BMSCs) down the chondrogenic lineage. Kindlin-3 expression increased with chondrogenic differentiation, similar to RUNX2. BMSCs isolated from a Kindlin-3 deficient patient expressed chondrocyte markers, including SOX9, under basal conditions, which were further enhanced with chondrogenic differentiation. Rescue of integrin activation by a constitutively activated β₃ integrin construct increasExperimental cell researchKindlin-3 mutation in mesenchymal stem cells results in enhanced chondrogenesis.PMC7874523R01 HL142772F32 CA142133R01 HL071625P01 HL073311K99 CA175291Kerr BAShi LWilley JSCaplan AIHarris KSByzova TVLennon DPJinnah AHfalseKindlin-3 mutation in mesenchymal stem cells results in enhanced chondrogenesis.Identifying patient mutations driving skeletal development disorders has driven our understanding of bone development. Integrin adhesion deficiency disease is caused by a Kindlin-3 (fermitin family member 3) mutation, and its inactivation results in bleeding disorders and osteopenia. In this study, we uncover a role for Kindlin-3 in the differentiation of bone marrow mesenchymal stem cells (BMSCs) down the chondrogenic lineage. Kindlin-3 expression increased with chondrogenic differentiation, similar to RUNX2. BMSCs isolated from a Kindlin-3 deficient patient expressed chondrocyte markers, including SOX9, under basal conditions, which were further enhanced with chondrogenic differentiation. Rescue of integrin activation by a constitutively activated β₃ integrin construct increas2021-01-01T00:00:00Z2021 Feb2025-04-03T23:32:22.956Z2025-04-03T23:32:22.956ZS-EPMC78745233341792110.1016/j.yexcr.2020.112456