2024 Volume No 47 – pages 142-151
Title: Noggin inhibits TGF-β1 OR TGF-β3 induced chondrogenesis of mesenchymal stromal cells |
Authors: L Wen, AR Armiento, AG Guex, S Grad, L Creemers, MJ Stoddart |
Address: AO Research Institute Davos, 7270 Davos Platz, Switzerland |
E-mail: martin.stoddart at aofoundation.org |
Abstract: Noggin (NOG) is an antagonist of bone morphogenetic proteins (BMPs), which regulates development and homeostasis of bone and cartilage. NOG has also been discovered to be an antagonist of transforming growth factor-β1 (TGF-β1). However, the effect of NOG on chondrogenesis induced by TGF-β1 remains unknown. Interestingly, in previous work NOG did not appear to influence TGF-β3-driven chondrogenesis, implying isoform specificity. In our study, the impact of exogenous NOG on TGF-β-induced chondrogenesis of bone marrow derived mesenchymal stromal cells (MSCs) was further investigated. Both TGF-β1 and TGF-β3 supplementation increased NOG expression at day 7, 14, 21 and 28 in MSC pellet culture. Addition of NOG during chondrogenic differentiation in vitro reduced sGAG release into the medium and retention within the pellet induced by TGF-β1 or TGF-β3. This was further confirmed by Safranin O/Fast Green staining. Gene downregulation including ACAN, COL2A1 and SOX9, was also observed downregulated by NOG at day 7. The same inhibitory role of NOG in TGF-β1 or TGF-β3-induced chondrogenesis suggests that the effect is not isoform-specific. We also observed differences mediated by NOG between the TGF-β1 and TGF-β3 groups. NOG suppresses cell proliferation during TGF-β1-induced chondrogenesis, whereas no significant alteration was observed in the TGF-β3 group. The effect of NOG on hypertrophy at day 7 was also investigated. In the TGF-β1 group, NOG resulted in alleviation of hypertrophy by downregulating COL10A1 and IHH expression. In the TGF-β3 group, NOG reduced hypertrophy through downregulation of COL10A1 and RUNX2. |
Keywords: Noggin, TGF-β1, TGF-β3, chondrogenesis, hypertrophy. |
Publication date: May 20th 2024 |
Copyright policy: © 2024 The Author(s). Published by Forum Multimedia Publishing, LLC. This article is distributed in accordance with Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/). |
Article download: Pages 142-151 (PDF file) |
