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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Emerging evidence indicates periostin (POSTN) is upregulated in patients with OA, and studies have shown that it can induce the activation of inflammatory cytokines and catabolic enzymes, making it a potential therapeutic target. Link N (LN) is a peptide fragment derived from the link protein and has been demonstrated as an anabolic-like factor and anti-catabolic and anti-inflammatory factors both in vitro and in vivo. This study aims to determine if LN can regulate POSTN expression and function in OA cartilage. Articular cartilage was recovered from donors undergoing total knee replacements to isolate chondrocytes and prepare osteochondral explants. Cells and explants were treated with POSTN and LN (1 and 100 μg) and measured for changes in POSTN expression and various matrix proteins, catabolic and proinflammatory factors, and signaling. To determine the effects of POSTN expression in vivo, a rabbit OA model was used. Immunoprecipitation and in silico modeling were used to determine peptide/POSTN interactions. Western blotting, PCR, and immunohistochemistry demonstrated that LN decreased POSTN expression both in vitro and in vivo. LN was also able to directly inhibit POSTN signaling in OA chondrocytes. In silico docking suggested the direct interaction of LN with POSTN at residues responsible for its oligomerization. Immunoprecipitation experiments confirmed the direct interaction of LN with POSTN and the destabilization of its oligomerization. This study demonstrates the ability of a peptide, LN, to suppress the overexpression and function of POSTN in OA cartilage.

Details

Title
Advances in the Regulation of Periostin for Osteoarthritic Cartilage Repair Applications
Author
Shih, Sunny Y 1 ; Grant, Michael P 1   VIAFID ORCID Logo  ; Epure, Laura M 2 ; Alad, Muskan 1 ; Lerouge, Sophie 3   VIAFID ORCID Logo  ; Huk, Olga L 2 ; Bergeron, Stephane G 2   VIAFID ORCID Logo  ; Zukor, David J 2 ; Merle, Géraldine 4   VIAFID ORCID Logo  ; Hee-Jeong Im 5   VIAFID ORCID Logo  ; Antoniou, John 1 ; Mwale, Fackson 1 

 Department of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, Canada[email protected] (G.M.); ; Orthopaedic Research Laboratory, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada 
 Department of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, Canada[email protected] (G.M.); ; Department of Orthopaedics, SMBD-Jewish General Hospital, McGill University, Montreal, QC H3T 1E2, Canada 
 Department of Mechanical Engineering, École de Technologie Supérieure (ETS), Montreal, QC H3C 1K3, Canada; Laboratory of Endovascular Biomaterials (LBeV), Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada 
 Department of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, Canada[email protected] (G.M.); ; Chemical Engineering Department, Polytechnique Montréal, Montreal, QC H3C 3A7, Canada 
 Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA; Jesse Brown Veterans Affairs Medical Center (JBVAMC), Chicago, IL 60612, USA 
First page
1469
Publication year
2024
Publication date
2024
Publisher
MDPI AG
e-ISSN
2218273X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3132985888
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.