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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Osteogenesis* ; Osteoclasts*; Hydrogels/pharmacology ; Peptides/pharmacology ; Actin Cytoskeleton

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.

Acta Biomater. 2022 Aug;148:1-21. (PMID: 35675889)
J Cell Physiol. 2019 Jul;234(7):11969-11975. (PMID: 30515780)
Biochem J. 2016 Apr 15;473(8):1001-25. (PMID: 27060106)
Bone Rep. 2016 Jul 19;5:214-221. (PMID: 28580389)
Gels. 2022 Dec 08;8(12):. (PMID: 36547328)
Nat Rev Bioeng. 2023 Apr 25;:1-19. (PMID: 37359773)
PLoS One. 2012;7(6):e37872. (PMID: 22701585)
Nanomaterials (Basel). 2020 Jul 31;10(8):. (PMID: 32752105)
Biology (Basel). 2021 Feb 04;10(2):. (PMID: 33557437)
Sensors (Basel). 2015 May 05;15(5):10481-510. (PMID: 25951336)
Acta Biomater. 2022 Jan 15;138:144-154. (PMID: 34781025)
Biophys J. 2016 Dec 6;111(11):2377-2386. (PMID: 27926839)
Nature. 2003 May 15;423(6937):337-42. (PMID: 12748652)
Nat Protoc. 2006;1(6):2891-9. (PMID: 17406548)
J Clin Invest. 2011 Sep;121(9):3505-16. (PMID: 21841309)
Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):1038-43. (PMID: 26744311)
J Exp Med. 2002 Jan 21;195(2):201-9. (PMID: 11805147)
Soft Matter. 2019 Feb 20;15(8):1704-1715. (PMID: 30724947)
J Bone Miner Res. 1991 Aug;6(8):817-26. (PMID: 1664645)
Biotechniques. 1991 Nov;11(5):620-7. (PMID: 1804254)
Blood. 2016 Feb 4;127(5):529-37. (PMID: 26552697)
Front Cell Dev Biol. 2021 Apr 12;9:641162. (PMID: 33912557)
Biomacromolecules. 2021 May 10;22(5):2094-2106. (PMID: 33908763)
J Cancer. 2021 May 5;12(13):3769-3780. (PMID: 34093786)
Bone. 2022 Jun;159:116353. (PMID: 35181574)
Electron Microsc Rev. 1991;4(1):1-45. (PMID: 1873485)
Curr Protein Pept Sci. 2000 Dec;1(4):349-84. (PMID: 12369905)
Bone. 2022 Nov;164:116538. (PMID: 36028118)
Joint Bone Spine. 2022 Oct;89(5):105400. (PMID: 35504517)
Nat Protoc. 2006;1(6):2876-90. (PMID: 17406547)
Int J Mol Sci. 2020 Aug 08;21(16):. (PMID: 32784443)
Eur J Immunol. 2016 Apr;46(4):952-63. (PMID: 26786702)
Curr Osteoporos Rep. 2007 Sep;5(3):98-104. (PMID: 17925190)
Gels. 2022 Apr 21;8(5):. (PMID: 35621553)

BB/S506692/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; BB/S507969/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; United Kingdom WT_ Wellcome Trust; MC_PC_19046 United Kingdom MRC_ Medical Research Council; MR/R105767/1 United Kingdom MRC_ Medical Research Council

Keywords: OSCAR receptor; bioactive motifs; osteoclast; osteoclastogenesis; peptide hydrogel

0 (Hydrogels)
0 (Peptides)

Date Created: 20240111 Date Completed: 20240112 Latest Revision: 20240210

20250114

PMC10779143

10.3390/ijms25010445

38203618