Osteoprotegerin is induced by transforming growth factor-beta 1 and regulates pro-fibrotic responses in human dermal fibroblasts
Transforming growth factor-beta1 (TGF-β1) is known to play a key role in the progression of organ fibrosis. Here, we demonstrate that TGF-β1 induces osteoprotegerin (OPG) expression in human dermal fibroblasts (HDFs) at both protein and mRNA levels. OPG neutralization has led to attenuation of TGF-β1-mediated profibrotic effects in HDFs. Further, we found that recombinant OPG induced fibronectin (FN) production and alpha-smooth muscle actin (α-SMA) expression. Interestingly, the OPG-mediated effect was significantly attenuated by αvβ3-integrin inhibitors (cyclo(RGDfK) and cilengitide) suggesting that OPG exerts profibrotic responses in human dermal fibroblasts by regulating αvβ3-integrin activation. Taken together, our data suggest that OPG expression is stimulated by TGF-β1 and contributes to dermal fibroblast activation.
Authors
- Santiago Sánchez (ORCID: https://orcid.org/0000-0002-8027-7661)
- Konstantin Tsoyi (ORCID: https://orcid.org/0000-0001-5843-5427)
- Alan Waich (ORCID: https://orcid.org/0000-0001-5426-4579)
- Aaron K McDowell-Sanchez
Institutions
- Baylor College of Medicine (US)
- Max Planck Florida Institute for Neuroscience (US)
Publication Details
- Journal
- Biochemical and Biophysical Research Communications
- Published
- 2025-02-21
- DOI
- https://doi.org/10.1016/j.bbrc.2025.151524
- Primary Topic
- Bone Metabolism and Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- National Institute of Arthritis and Musculoskeletal and Skin Diseases