KLF15 regulates in vitro chondrogenic differentiation of human mesenchymal stem cells by targeting SOX9

Mesenchymal stem cells (MSCs) are multipotent stromal cells residing in the bone marrow. MSCs have the potential to differentiate into adipocytes, chondrocytes, and other types of cells. However, the mechanism underlying MSC differentiation is still not fully understood. Here we aimed to investigate the function of the Kruppel-like factor (KLF) transcriptional factor family in regulating chondrogenic differentiation from human MSCs. Among the KLF family members, KLF15 was activated during different models of chondrogenic differentiation in a time-dependent manner. Lentivirus-mediated knockdown of KLF15 in MSCs repressed chondrogenic differentiation whereas KLF15 overexpression facilitated chondrogenic differentiation. KLF15 promoted the chondrogenic differentiation of human MSCs by activating the expression of SOX9, which is critically involved in KLF15 function during chondrogenic differentiation. Our mechanism study demonstrated that KLF15 bound the promoter of SOX9 and promoted the activation of the SOX9 promoter. Taken together, our findings show that KLF15 promotes chondrogenic differentiation of human MSCs by activating SOX9.