The Low expression of PAI-1 increasing MC3T3-E1 cell proliferation by promoting glucose metabolism and activating BMP/TGF-β/Smad and Wnt/β-catenin pathways: a downstream regulatory role of PAI-1 in osteoblasts

Abstract

Abstract PAI-1 is a marker of aging and a mediator of aging induction. Our previous study showed that PAI-1 is highly expressed in bone tissues of osteoporosis patients. Gavage of osteoporosis model mice with PAI-1 inhibitor resulted in increased Osteoblasts and bone mineral density. Inhibition of PAI-1 expression in MC3T3-E1 cells found that the altered transcription factors were mainly enriched in zf-C2H2 (12.38%) and HMG (10.48%), and Zinc finger related proteins were significantly increased in the differential proteins. Transcription factors use the energy provided by ATP to regulate the transcription and translation of downstream genes. The low expression of PAI-1 in MC3T3-E1 cells promotes ATP synthesis, cell cycle progression through cellular ATP binding and cellular metabolic process, and as a result, Osteoblast proliferation. Runx1 is expressed at different stages of Chondrocyte and Osteoblast differentiation and promotes Chondrogenesis by regulating the BMP/TGF-β/Smad and Wnt/β-catenin signaling pathways. The low expression of PAI-1 in MC3T3-E1 cells promotes Runx1 expression. This may imply that the low expression of PAI-1 may promote Osteoblast proliferation by activating the BMP/TGF-β/Smad and Wnt/β-catenin pathways by Runx1.