The PPAR-γ/SFRP5/Wnt/β-catenin signal axis regulates the dexamethasone-induced osteoporosis. (July 2021)

• Record Type: Journal Article
• Authors: He, Hai-Peng; Gu, Shan
• Is Part Of: Cytokine. Volume 143(2021)
• Publication Date: 2021-07
• Subjects: PPAR-γ -- SFRP5 -- Osteoblastic differentiation -- Wnt/β-catenin signaling pathway; PPAR-γ peroxisome proliferator-activated receptor-gamma -- SFRP5 secreted frizzled-related protein5 -- rBMSC rat bone marrow mesenchymal stem cell -- Dex dexamethasone -- BMD bone mineral density -- SFRPs secreted frizzled-related proteins family -- FBS Fetal Bovine Serum -- PBS phosphate-buffered saline -- RUNX2 Runt-related transcription factor-2 -- ALP alkaline phosphatases -- OPN osteopontin -- RT-qPCR real-time quantitative polymerase chain reaction -- SDS-PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis -- ARS Alizarin Red S -- shRNA short hairpin RNA -- SD standard deviation -- GC glucocorticoid -- GADPH glyceraldehyde-3-phosphate dehydrogenase -- Wnt Wingless-type -- GSK-3β glycogen synthase kinase-3β -- OIM osteogenic induction medium -- DMEM Dulbecco's modified eagle medium -- NC negative control; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2021.155488
• Languages: English
• ISSNs: 1043-4666

Abstract

Abstract: Background: The inhibition of glucocorticoid (GC) on osteoblastic differentiation of bone marrow stromal stem cells (BMSC) is an important pathway for GC to reduce bone formation. Recent studies implicated an important role of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in GC-mediated cell proliferation and differentiation. Thus, our purpose is to investigate the role of PPAR-γ in regulating rat BMSC (rBMSC) osteoblastic differentiation. Methods: The rBMSC treated with dexamethasone (Dex) was used to construct an in vitro cell model of GC-induced osteoporosis. The expressions of PPAR-γ, RUNX2, ALP, OPN and SFRP5 in cells were detected by RT-qPCR and western blot assays. Osteogenic differentiation of rBMSC was measured by Alizarin Red S (ARS) staining analysis. Lentivirus-delivered shRNA was used to knock down PPAR-γ or SFRP5, and lentivirus-delivered constructs were used to overexpress SFRP5 in rBMSC to verify the effect of PPAR-γ or SFRP5 on cell osteogenic differentiation. Results: Dex significantly reduced rBMSC osteoblastic differentiation. The expression of PPAR-γ was enhanced in Dex treated rBMSC. PPAR-γ down-regulation improved Dex inhibition of rBMSC osteogenic differentiation. Moreover, PPAR-γ knockdown promoted protein levels of RUNX2, ALP, OPN and Dex-decreased rBMSC osteogenic differentiation. The expression of SFRP5 was reduced while Wnt and β-catenin were increased in PPAR-γ knockdown and Dex treated rBMSC. Moreover, the up-regulation of SFRP5 reversed the osteogenic differentiation of rBMSC induced by PPAR-γ knockdown. Conclusion: These data indicated that in GC-induced osteoporosis, PPAR-γ/SFRP5 affects osteogenic differentiation by regulating the Wnt/β-catenin signaling pathway.