Krüppel-like factor 4 regulates cellular proliferation and differentiation in human bone marrow-derived mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) form one of the types of adult stem cell which have the capacity to self-renew, and the multipotentiality for osteogenic, chondrogenic and adipogenic differentiation and immune modulation. Consequently, MSCs are an attractive cell source for regenerative medicine and therapy for inflammatory disease. However, biological criteria to ensure any particular MSCs are “stem cells” have not been clarified. Previously, we reported that MSCs isolated from a single CD90/CD271 double-positive cell in human bone marrow have high colony-forming capacity and tri-lineage differentiation potential in vitro. Such clonal MSCs are highly homogeneous and considered to be useful for the analysis of molecular function. In this study, we focused on Krüppel-like factor 4 (KLF4) which is highly expressed by our MSC subtype, and examined its role in vitro. The expression of KLF4 was significantly reduced within 24 h after the induction of adipogenic or osteogenic differentiation. Knockdown of KLF4 led to promotion of cellular proliferation and differentiation at an early stage. Furthermore, the expressions of TGFBR1, FZD6, FGFR2, THY1 and CXCL12 genes were upregulated in KLF4 knockdown MSCs. These results indicated that KLF4 regulates not only cellular proliferation but also the early stage of differentiation. Our findings suggest that KLF4 has an important role in maintaining the properties of MSCs and regulating differentiation via TGF-β, WNT and FGF signaling pathways.