Collagen-like Osteoclast-Associated Receptor (OSCAR)-Binding Motifs Show a Co-Stimulatory Effect on Osteoclastogenesis in a Peptide Hydrogel System

Vitale, Mattia; Ligorio, Cosimo; Richardson, Stephen M.; Hoyland, Judith A.; Bella, Jordi

Abstract

Osteoclastogenesis, one of the dynamic pathways underlying bone remodelling, is a complex process that includes many stages. This complexity, while offering a wealth of therapeutic opportunities, represents a substantial challenge in unravelling the underlying mechanisms. As such, there is a high demand for robust model systems to understand osteoclastogenesis. Hydrogels seeded with osteoclast precursors and decorated with peptides or proteins mimicking bone’s extracellular matrix could provide a useful synthetic tool to study pre-osteoclast-matrix interactions and their effect on osteoclastogenesis. For instance, fibrillar collagens have been shown to provide a co-stimulatory pathway for osteoclastogenesis through interaction with the osteoclast-associated receptor (OSCAR), a regulator of osteoclastogenesis expressed on the surface of pre-osteoclast cells. Based on this rationale, here we design two OSCAR-binding peptides and one recombinant OSCAR-binding protein, and we combine them with peptide-based hydrogels to study their effect on osteoclastogenesis. The OSCAR-binding peptides adopt the collagen triple-helical conformation and interact with OSCAR, as shown by circular dichroism spectropolarimetry and surface plasmon resonance. Furthermore, they have a positive effect on osteoclastogenesis, as demonstrated by appropriate gene expression and tartrate-resistant acid phosphatase staining typical of osteoclast formation. Combination of the OSCAR-binding peptides or the OSCAR-binding recombinant protein with peptide-based hydrogels enhances osteoclast differentiation when compared to the non-modified hydrogels, as demonstrated by multi-nucleation and by F-actin staining showing a characteristic osteoclast-like morphology. We envisage that these hydrogels could be used as a platform to study osteoclastogenesis and, in particular, to investigate the effect of costimulatory pathways involving OSCAR.

Citation

Vitale, M., Ligorio, C., Richardson, S. M., Hoyland, J. A., & Bella, J. (2023). Collagen-like Osteoclast-Associated Receptor (OSCAR)-Binding Motifs Show a Co-Stimulatory Effect on Osteoclastogenesis in a Peptide Hydrogel System. International Journal of Molecular Sciences, 25(1), Article 445. https://doi.org/10.3390/ijms25010445

• Journal Article Type: Article
• Acceptance Date: Dec 25, 2023
• Online Publication Date: Dec 28, 2023
• Publication Date: Dec 28, 2023
• Deposit Date: Mar 25, 2024
• Publicly Available Date: Mar 26, 2024
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 1
• Article Number: 445
• DOI: https://doi.org/10.3390/ijms25010445
• Keywords: osteoclastogenesis, bioactive motifs, OSCAR receptor, osteoclast, peptide hydrogel
• Public URL: https://nottingham-repository.worktribe.com/output/29826048
• Publisher URL: https://www.mdpi.com/1422-0067/25/1/445