Effect of Liver Kinase B1 on Osteogenesis and Lipogenesis Differentiation of Bone Marrow Mesenchymal Stem Cells Under Oxidative Stress

The proliferation of bone marrow mesenchymal stem cells (BMSCs) is suppressed during oxidative stress (OS). Liver kinase B1 (LKB1) participates in cell proliferation and apoptosis. However, the effect of LKB1 on osteogenesis or lipogenesis differentiation of BMSCs under OS conditions remains unclear. In vitro cultured BMSCs were divided into three groups: control group, OS model group prepared by H2O2, and LKB1 siRNA group in which OS treated cells received siRNA transfection. Real-time fluorescent PCR and Western blot were used to analyze LKB1 expression. Real-time PCR was used to measure the mRNA expression of osteogenesis related genes including osteocalcin, type I collagen, RUNX2 and OPN. Western blot was used to analyze the protein expression of lipogenesis specific differentiation genes FABP4 and critical transcriptional regulator PPAR gamma 2. In OS group, mRNA and protein expression of LKB1 were significantly increased, the mRNA expression of osteocalcin, type I collagen, RUNX2 and OPN was reduced, and the protein expression of FABP4 and PPAR gamma 2 was increased (P < 0.05 comparing to control group). Transfection of LKB1 siRNA into BMSCs under OS condition decreased the mRNA and protein expression of LKB1, increased the mRNA expression of osteocalcin, type I collagen, RUNX2 and OPN mRNA, as well as decreased the protein expression of FABP4 and PPAR gamma 2 (P < 0.05 comparing to OS group). OS can facilitate LKB1 expression, inhibit osteogenesis differentiation of BMSCs, and promote lipogenesis differentiation. Down-regulation of LKB1 expression facilitates osteogenesis differentiation and inhibits lipogenesis differentiation.