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Home / Equine Research Bank / J Orthop Res / Matrikine stimulation of equine synovial fibroblasts and cho...
Journal of orthopaedic research : official publication of the Orthopaedic Research Society2024; doi: 10.1002/jor.26004

Matrikine stimulation of equine synovial fibroblasts and chondrocytes results in an in vitro osteoarthritis phenotype.

Abstract: Osteoarthritis (OA) is a debilitating disease that impacts millions of individuals and has limited therapeutic options. A significant hindrance to therapeutic discovery is the lack of in vitro OA models that translate reliably to in vivo preclinical animal models. An alternative to traditional inflammatory cytokine models is the matrikine stimulation model, in which fragments of matrix proteins naturally found in OA tissues and synovial fluid, are used to stimulate cells of the joint. The objective of this study was to determine if matrikine stimulation of equine synovial fibroblasts and chondrocytes with fibronectin fragments (FN7-10) would result in an OA phenotype. We hypothesized that FN7-10 stimulation of equine articular cells would result in an OA phenotype with gene and protein expression changes similar to those previously described for human chondrocytes stimulated with FN7-10. Synovial fibroblasts and chondrocytes isolated from four horses were stimulated in monolayer culture for 6 or 18 h with 1 µM purified recombinant 42 kD FN7-10 in serum-free media. At the conclusion of stimulation, RNA was collected for targeted gene expression analysis and media for targeted protein production analysis. Consistent with our hypothesis, FN7-10 stimulation resulted in significant alterations to many important genes that are involved in OA pathogenesis including increased expression of IL-1β, IL-4, IL-6, CCL2/MCP-1, CCL5/RANTES, CXCL6/GCP-2, MMP-1, MMP-3, and MMP13. The results of this study suggest that the equine matrikine stimulation model of OA may prove useful for in vitro experiments leading up to preclinical trials.
© 2024 The Author(s). Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.
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Publication Date: 2024-11-01 PubMed ID: 39486895DOI: 10.1002/jor.26004Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article explores the use of matrikine stimulation to create a reliable in vitro model of osteoarthritis (OA) using equine synovial fibroblasts and chondrocytes. The researchers found encouraging results with gene and protein expression changes similar to those in OA, suggesting this method may be helpful in developing new therapeutics.

Overview and Objectives

  • This research study aimed to advance therapeutic discovery for osteoarthritis (OA), a disease with limited treatment options affecting millions of people around the world. More specifically, the described research sought to develop a reliable in vitro model of OA that would be applicable to in vivo preclinical animal testing.
  • Instead of the traditional inflammatory cytokine models, researchers employed the matrikine stimulation model. This model involves using fragments of matrix proteins, known as matrikines, which are naturally found in OA-perturbed tissues and synovial fluid, to stimulate cells of the joint.
  • The precise intent of this study was to find out whether matrikine stimulation of equine synovial fibroblasts and chondrocytes with fibronectin fragments (FN7-10) could create an OA phenotype. The assumption was that FN7-10 stimulation of joint cells would result in an OA phenotype with gene and protein expression changes that were alike to those in human chondrocytes stimulated with FN7-10.

Methodology

  • The researchers used synovial fibroblasts and chondrocytes isolated from horses and stimulated them in monolayer culture for either 6 or 18 hours using 1 µM of purified recombinant 42 kD FN7-10 within serum-free media.
  • After stimulation, RNA was gathered for targeted gene expression analysis, and media collected for targeted protein production analysis.

Findings and Implications

  • As hypothesized, FN7-10 stimulation led to significant changes in genes involving OA pathogenesis. These changes were seen as an increased expression in several important genes, including IL-1β, IL-4, IL-6, CCL2/MCP-1, CCL5/RANTES, CXCL6/GCP-2, MMP-1, MMP-3, and MMP13. These results were in line with what was seen in human chondrocytes stimulated with FN7-10.
  • The findings of this study suggest the equine matrikine stimulation model of OA could be beneficial for in vitro experiments preceding preclinical trials. This development may potentially contribute to expanding therapeutic options for patients with OA.

Cite This Article

APA
Gagliardi R, Koch DW, Loeser R, Schnabel LV. (2024). Matrikine stimulation of equine synovial fibroblasts and chondrocytes results in an in vitro osteoarthritis phenotype. J Orthop Res. https://doi.org/10.1002/jor.26004

Publication

Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
NlmUniqueID: 8404726
Country: United States
Language: English

Researcher Affiliations

Gagliardi, Rachel
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA.
Koch, Drew W
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA.
Loeser, Richard
  • Division of Rheumatology, Allergy and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
  • Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Schnabel, Lauren V
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA.
  • Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.

Grant Funding

  • F.O.R.G.E. Fund
  • T32OD011130 / ORIP NIH HHS
  • Intramural / College of Veterinary Medicine, North Carolina State University
  • R37 AR049003 / NIAMS NIH HHS

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