Atsttrin Regulates Osteoblastogenesis and Osteoclastogenesis through TNFR Pathway

Abstract

Abstract Osteoporosis is a systemic metabolic bone disease. Osteoporosis is believed to be a systemic inflammatory condition in which inflammatory cytokines play an important role. Among these molecules, tumor necrosis factor-α (TNF-α) plays an important role in the initiation and development of osteoporosis. Atsttrin is an engineered protein derived from the growth factor, progranulin (PGRN). It’s well accepted Atsttrin inhibits TNF-α’s function by binding tumor necrosis factor-α receptors (TNFRs). The aim of this study was to investigate the role of Atsttrin in osteoporosis. Present study use cell TRAP staining to determine the role of Atsttrin in osteoclastogenesis. Alkaline phosphatase staining of cells was examined for ostoblastogenesis. Western blotting and ELISA assay were taken for the measurement of protein level and phorsphorylation. Real time PCR was used to test the transcriptional level expression. Gene silence method was taken for the pathway investigation. By applying these methods, we found Atsttrin inhibited TNF-α-induced osteoclastogenesis and inflammatory destruction. Further mechanism studies indicated Atsttrin inhibited TNF-α- induced osteoclastogenesis though TNFR1 signaling pathway. Moreover, Atsttrin rescued TNF-α-mediated inhibition of osteoblastogenesis via TNFR1 pathway. Importantly, present study found Atsttrin could not induce osteoblast differentiation, however, Atsttrin could significantly enhance osteoblastogenesis through TNFR2-Akt-Erk1/2 signaling.