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Nerve growth factor receptors in equine synovial membranes vary with osteoarthritic disease severity.

Abstract: Nerve growth factor (NGF) is a neurotrophin that has been implicated in pain signaling, apoptosis, inflammation and proliferation. The resultant effects depend on interaction with two different receptors; tyrosine kinase A (TrkA) and p75 . NGF increases in synovial fluid from osteoarthritic joints, and monoclonal antibody therapy is trialed to treat osteoarthritis (OA)-related pain. Investigation of the complex and somewhat contradictory signaling pathways of NGF is conducted in neural research, but has not followed through to orthopaedic studies. The objectives of this study were to compare the expression of NGF receptors and the downstream regulator BAX in synovial membranes from joints in various stages of OA. The horse was used as a model. Synovial membranes were harvested from five healthy horses postmortem and from clinical cases with spontaneous OA undergoing arthroscopic surgery for lameness. Four horses with synovitis without gross cartilage changes, four horses with synovitis and cartilage damage, and four horses with synovitis and intracarpal fractures were included. Samples were investigated by immunohistochemistry and results showed that nuclear staining of TrkA, p75 and BAX increases in OA-associated synovitis. TrkA expression increased in early disease stages whereas increases in p75 were most prominent in later disease stages with cartilage damage and fibrosis. Clinical significance: Suppression of NGF may result in varied effects depending on different stages of the osteoarthritic disease process.
Publication Date: 2022-05-31 PubMed ID: 35578994PubMed Central: PMC10084167DOI: 10.1002/jor.25382Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research article investigates how the nerve growth factor (NGF) receptors present in horse synovial membranes react differently based on osteoarthritic disease severity.

Objective of the Research

  • The primary aim of this study was to examine the differences in the expression of NGF receptors and their downstream regulator BAX in synovial membranes found in horse joints at varying levels of Osteoarthritis (OA).

About Nerve Growth Factor (NGF)

  • NGF is a neurotrophin, a kind of protein that plays a crucial role in the survival and maturation of certain nerve cells. It’s implicated in a number of biological processes such as pain signaling, apoptosis (programmed cell death), inflammation, and cell growth. The effects it induces depend on its interaction with two different receptors – tyrosine kinase A (TrkA) and p75.
  • The levels of NGF in the synovial fluid (a kind of lubricating fluid present in the joints) are found to increase in osteoarthritic joints. As a result, therapies using monoclonal antibodies to suppress the effects of NGF are currently being tested for pain management in osteoarthritis.

Methodology and Findings of the Study

  • The study was performed using the synovial membranes taken from the joint of horses undergoing different stages of osteoarthritis. The samples were obtained from five healthy horses postmortem and from various clinical cases with spontaneous OA undergoing arthroscopic surgery due to lameness.
  • The samples were then examined under immunohistochemistry, a technique used to visualize specific proteins in cells of a tissue section using antibodies against them. The results indicated an increase in the nuclear staining of TrkA, p75, and BAX in synovitis associated with OA.
  • The investigation discovered that TrkA’s expression increases in the early stages of the disease, whereas the rise in p75 was more noticeable in later stages, specifically when cartilage damage and fibrosis occurred.

Clinical Significance

  • The findings from this research suggest that suppressing NGF might lead to various effects depending on the particular stages of the osteoarthritic disease process. Consequently, a more detailed understanding of the function and regulation of these receptors might help develop new strategies to manage osteoarthritic pain based on disease severity.

Cite This Article

APA
Kendall A, Ekman S, Skiöldebrand E. (2022). Nerve growth factor receptors in equine synovial membranes vary with osteoarthritic disease severity. J Orthop Res, 41(2), 316-324. https://doi.org/10.1002/jor.25382

Publication

ISSN: 1554-527X
NlmUniqueID: 8404726
Country: United States
Language: English
Volume: 41
Issue: 2
Pages: 316-324

Researcher Affiliations

Kendall, Anna
  • Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Ekman, Stina
  • Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Skiöldebrand, Eva
  • Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.

MeSH Terms

  • Horses
  • Animals
  • Receptor, trkA / metabolism
  • Nerve Growth Factor / metabolism
  • bcl-2-Associated X Protein
  • Receptors, Nerve Growth Factor / metabolism
  • Synovial Membrane / metabolism
  • Osteoarthritis
  • Synovitis
  • Pain
  • Patient Acuity

Conflict of Interest Statement

The authors declare no conflict of interest.

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