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Home / Equine Research Bank / Vet Anim Sci / Serotonin-evoked cytosolic Ca2+ release and opioid receptor ...
Veterinary and animal science2019; 8; 100078; doi: 10.1016/j.vas.2019.100078

Serotonin-evoked cytosolic Ca2+ release and opioid receptor expression are upregulated in articular cartilage chondrocytes from osteoarthritic joints in horses.

Abstract: Osteoarthritis is a pain-associated progressive disease and pain mediators, such as opioid receptors, expressed in articular cartilage could represent novel therapeutic targets. Acute and chronic stages of OA indicate different metabolic abilities of the chondrocytes depending on inflammatory state. This study aimed to investigate the response of healthy and osteoarthritic chondrocytes and their expression and release of pain mediators in response to acute inflammation. Interleukin-1 beta (IL-1β) and lipopolysaccharide (LPS) were used to induce an acute inflammatory response in cultured equine chondrocytes harvested from healthy joints (HC) and osteoarthritic joints (OAC), the latter representing acute exacerbation of a chronic inflammatory state. Intracellular Ca release was determined after exposure to serotonin (5-hydroxytryptamine (5-HT), glutamate or ATP. Protein expression levels of F- and G-actin, representing actin rearrangement, and opioid receptors were investigated. Glutamate concentrations in culture media were measured. Cartilage was immunohistochemically stained for µ (MOR), κ (KOR), and δ (DOR) opioid receptors. Upon exposure to acute inflammatory stimuli, OAC showed increased intracellular Ca release after 5-HT stimulation and increased expression of MOR and KOR. When cells were stimulated by inflammatory mediators, glutamate release was increased in both HC and OAC. Immunostaining for MOR was strong in OA cartilage, whereas KOR was less strongly expressed. DOR was not expressed by cultured HC and OAC and immunostaining of OA cartilage equivocal. We show that chondrocytes in different inflammatory stages react differently to the neurotransmitter 5-HT with respect to intracellular Ca release and expression of peripheral pain mediators. Our findings suggest that opioids and neurotransmitters are important in the progression of equine OA. The inflammatory stage of OA (acute chronic) should be taken into consideration when therapeutic strategies are being developed.
© 2019 The Author(s).
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Publication Date: 2019-09-27 PubMed ID: 32734095PubMed Central: PMC7386637DOI: 10.1016/j.vas.2019.100078Google Scholar: Lookup
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  • Journal Article

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.

The research article investigates the differing response of healthy and osteoarthritic cells, notably their expression and release of pain mediators during acute inflammation. The study finds that inflammation stages play a role in these cells’ reactions to pain neurotransmitters, suggesting a need to consider these stages when developing OA therapy strategies.

Research Purpose and Methods

  • The research aims to observe the behavior of both healthy and osteoarthritic chondrocytes (cartilage cells) during an acute inflammatory response. How these cells respond, especially how they express and release pain mediators, is under scrutiny.
  • Chondrocytes from both healthy joints (HC) and osteoarthritic joints (OAC) were put through acute inflammatory simulation using Interleukin-1 beta (IL-1β) and lipopolysaccharide (LPS).
  • The researchers then analyzed the cells’ reaction to different hormones like serotonin (5-hydroxytryptamine (5-HT), glutamate or ATP.

Key Findings

  • The experiments revealed that OAC, indicative of naturally occurring chronic inflammation being acutely exacerbated, displayed an uptick in internal calcium release following 5-HT stimulation. Additionally, there was increased expression of µ (MOR) and κ (KOR) opioid receptors.
  • Under the influence of the inflammatory prods, both HC and OAC amplified their glutamate release.
  • Immunostaining allowed investigators to visualize that MOR was highly expressed in osteoarthritic cartilage, while KOR though present, had less vigorous expression. δ (DOR) opioid receptors weren’t shown by healthy or osteoarthritic cultured specimens.

Research Implications

  • The researchers conclude that different inflammatory stages make chondrocytes more or less sensitive to the neurotransmitter 5-HT in terms of internal calcium release and peripheral pain mediators’ expression.
  • The research suggests that neurotransmitters and opioids play a vital role in the advancement of equine osteoarthritis (OA).
  • It highlights a need to consider the inflammatory stage (acute vs chronic) when creating therapeutic strategies for OA.

Cite This Article

APA
Skiöldebrand E, Ley C, Björklund U, Lindahl A, Hansson E. (2019). Serotonin-evoked cytosolic Ca2+ release and opioid receptor expression are upregulated in articular cartilage chondrocytes from osteoarthritic joints in horses. Vet Anim Sci, 8, 100078. https://doi.org/10.1016/j.vas.2019.100078

Publication

Veterinary and animal science
ISSN: 2451-943X
NlmUniqueID: 101694897
Country: Netherlands
Language: English
Volume: 8
Pages: 100078
PII: 100078

Researcher Affiliations

Skiöldebrand, Eva
  • Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
  • Section of Pathology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Ley, Cecilia
  • Section of Pathology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Björklund, Ulrika
  • Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
Lindahl, Anders
  • Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
Hansson, Elisabeth
  • Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.

Conflict of Interest Statement

None of the authors has any financial or personal relationship that could inappropriately influence or bias the content of the paper. The authors have no conflict of interest

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Citations

This article has been cited 2 times.
  1. Cai L, Huang N, Zhang X, Wu S, Wang L, Ke Q. Long non-coding RNA plasmacytoma variant translocation 1 and growth arrest specific 5 regulate each other in osteoarthritis to regulate the apoptosis of chondrocytes.. Bioengineered 2022 May;13(5):13680-13688.
    doi: 10.1080/21655979.2022.2063653pubmed: 35706414google scholar: lookup
  2. Hansson E, Skiöldebrand E. Bupivacaine in combination with sildenafil (Viagra) and vitamin D3 have anti-inflammatory effects in osteoarthritic chondrocytes.. Curr Res Pharmacol Drug Discov 2021;2:100066.
    doi: 10.1016/j.crphar.2021.100066pubmed: 34909684google scholar: lookup
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