Osteopontin Upregulation, Induced by the Continuous Mechanical Load in Adipose Tissue-Derived Mesenchymal Stem Cells, is Strongly Restricted in INF-γ/TNF-α/IL-22 Microenvironment.

Autor: Shouval A; Rheumatology Unit, Bnai Zion Medical Center, 47 Golomb St, 38041, Haifa, Israel., Brant-Roznavi M; Department of Orthdontics and Craniofacial Anomalies, School of Graduate Dentistry, Rambam Health Care Campus, Haifa, Israel.; Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel., Tamari T; Department of Orthdontics and Craniofacial Anomalies, School of Graduate Dentistry, Rambam Health Care Campus, Haifa, Israel., Hazan-Molina H; Department of Orthdontics and Craniofacial Anomalies, School of Graduate Dentistry, Rambam Health Care Campus, Haifa, Israel.; Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel., Aizenbud D; Department of Orthdontics and Craniofacial Anomalies, School of Graduate Dentistry, Rambam Health Care Campus, Haifa, Israel.; Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel., Keret S; Rheumatology Unit, Bnai Zion Medical Center, 47 Golomb St, 38041, Haifa, Israel., Saiegh L; Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.; Endocrinology Department, Bnai Zion Medical Center, Haifa, Israel., Slobodin G; Rheumatology Unit, Bnai Zion Medical Center, 47 Golomb St, 38041, Haifa, Israel. gleb.slobodin@gmail.com.; Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. gleb.slobodin@gmail.com.
Jazyk: angličtina
Zdroj: Inflammation [Inflammation] 2023 Dec; Vol. 46 (6), pp. 2270-2275. Date of Electronic Publication: 2023 Jul 24.
DOI: 10.1007/s10753-023-01876-5
Abstrakt: The osteogenic potential of mesenchymal stem cells (MSc) in axial spondyloarthritis (AxSpA) depends on the interplay of inflammation and multiple hormonal and local mechanical factors. In this study, MCs, derived from the adipose tissue of a healthy donor, were cultured under or without continuous mechanical load in the osteogenic differentiation medium with or without the addition of testosterone, cocktail of INF-γ/TNF-α/IL-22, or both. Real-time PCR for osteogenic transcription factors demonstrated that in the absence of INF-γ/TNF-α/IL-22, mechanical load causes significant upregulation of SPP1 (osteopontin), while the presence of the inflammatory cytokines almost completely abolishes this effect. In addition, exposure to INF-γ/TNF-α/IL-22 slightly upregulated BMP2, but suppressed the expression of ALPL, Col1A1, and SPP1, reinforcing the hypothesis that the inflammatory environment allows MSc to commit toward the IL-22-driven osteogenic differentiation but can restrict the later stages of osteogenesis. In summary, osteopontin can play a role in the pathogenesis of AxSpA, linking between mechanical load and pathological bone formation.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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