| First Author | Kerr BA | Year | 2021 |
| Journal | Exp Cell Res | Volume | 399 |
| Issue | 2 | Pages | 112456 |
| PubMed ID | 33417921 | Mgi Jnum | J:306698 |
| Mgi Id | MGI:6707134 | Doi | 10.1016/j.yexcr.2020.112456 |
| Citation | Kerr BA, et al. (2021) Kindlin-3 mutation in mesenchymal stem cells results in enhanced chondrogenesis. Exp Cell Res 399(2):112456 |
| abstractText | 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 beta3 integrin construct increased adhesion to multiple extracellular matrices and reduced SOX9 expression to basal levels. Growth plates from mice expressing a mutated Kindlin-3 with the integrin binding site ablated demonstrated alterations in chondrocyte maturation similar to that seen with the human Kindlin-3 deficient BMSCs. These findings suggest that Kindlin-3 expression mirrors RUNX2 during chondrogenesis. |
