Advances in the Regulation of Periostin for Osteoarthritic Cartilage Repair Applications
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 ha...
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| Format: | Article |
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MDPI AG
2024-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/14/11/1469 |
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| author | Sunny Y. Shih Michael P. Grant Laura M. Epure Muskan Alad Sophie Lerouge Olga L. Huk Stephane G. Bergeron David J. Zukor Géraldine Merle Hee-Jeong Im John Antoniou Fackson Mwale |
| author_facet | Sunny Y. Shih Michael P. Grant Laura M. Epure Muskan Alad Sophie Lerouge Olga L. Huk Stephane G. Bergeron David J. Zukor Géraldine Merle Hee-Jeong Im John Antoniou Fackson Mwale |
| author_sort | Sunny Y. Shih |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6f1725b3c8bf47e9b39ea508d9c65c23 |
| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-6f1725b3c8bf47e9b39ea508d9c65c232025-08-20T02:28:11ZengMDPI AGBiomolecules2218-273X2024-11-011411146910.3390/biom14111469Advances in the Regulation of Periostin for Osteoarthritic Cartilage Repair ApplicationsSunny Y. Shih0Michael P. Grant1Laura M. Epure2Muskan Alad3Sophie Lerouge4Olga L. Huk5Stephane G. Bergeron6David J. Zukor7Géraldine Merle8Hee-Jeong Im9John Antoniou10Fackson Mwale11Department of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, CanadaDepartment of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, CanadaDepartment of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, CanadaDepartment of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, CanadaDepartment of Mechanical Engineering, École de Technologie Supérieure (ETS), Montreal, QC H3C 1K3, CanadaDepartment of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, CanadaDepartment of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, CanadaDepartment of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, CanadaDepartment of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, CanadaDepartment of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USADepartment of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, CanadaDepartment of Surgical and Interventional Sciences, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, CanadaEmerging 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.https://www.mdpi.com/2218-273X/14/11/1469periostincartilagechondrocyteLink Nosteoarthritis |
| spellingShingle | Sunny Y. Shih Michael P. Grant Laura M. Epure Muskan Alad Sophie Lerouge Olga L. Huk Stephane G. Bergeron David J. Zukor Géraldine Merle Hee-Jeong Im John Antoniou Fackson Mwale Advances in the Regulation of Periostin for Osteoarthritic Cartilage Repair Applications Biomolecules periostin cartilage chondrocyte Link N osteoarthritis |
| title | Advances in the Regulation of Periostin for Osteoarthritic Cartilage Repair Applications |
| title_full | Advances in the Regulation of Periostin for Osteoarthritic Cartilage Repair Applications |
| title_fullStr | Advances in the Regulation of Periostin for Osteoarthritic Cartilage Repair Applications |
| title_full_unstemmed | Advances in the Regulation of Periostin for Osteoarthritic Cartilage Repair Applications |
| title_short | Advances in the Regulation of Periostin for Osteoarthritic Cartilage Repair Applications |
| title_sort | advances in the regulation of periostin for osteoarthritic cartilage repair applications |
| topic | periostin cartilage chondrocyte Link N osteoarthritis |
| url | https://www.mdpi.com/2218-273X/14/11/1469 |
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