The PPAR-γ/SFRP5/Wnt/β-catenin signal axis regulates the dexamethasone-induced osteoporosis
| Autor: | Shan Gu, Hai-Peng He |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Stromal cell Transcription Genetic Immunology Peroxisome proliferator-activated receptor Biochemistry Models Biological Dexamethasone Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Adipokines Osteogenesis Immunology and Allergy Animals Molecular Biology Wnt Signaling Pathway chemistry.chemical_classification Gene knockdown Cell growth Wnt signaling pathway Cell Differentiation Mesenchymal Stem Cells Hematology Cell biology Rats RUNX2 PPAR gamma 030104 developmental biology chemistry 030220 oncology & carcinogenesis Catenin Gene Knockdown Techniques Osteoporosis Female Stem cell |
| Zdroj: | Cytokine. 143 |
| ISSN: | 1096-0023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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