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Journal of equine veterinary science2021; 103; 103643; doi: 10.1016/j.jevs.2021.103643

Aggrecan, IL-1β, IL-6, and TNF-α profiles in the Articular Cartilage of Miniature Horses with Chondrodysplastic Dwarfism.

Abstract: Dwarfism is a skeletal disorder that causes abnormal growth. In Miniature horses, dwarfism can occur as chondrodysplastic dwarfism, an autosomal recessive disorder associated with five mutations (D1, D2, D3*, D4 and c.6465A > T variant) in the aggrecan (ACAN) gene. The aim of this study was to evaluate the expression of aggrecan (at the gene and protein level) and specific cytokines (IL-1β, IL-6, and TNF-α) in the articular cartilage of Miniature horses with chondrodysplastic dwarfism (D4/c.6465A > T genotype). Metatarsal bone samples from eight dwarf Miniature horses were collected for histopathological analysis, and articular cartilage was collected to detect and quantify aggrecan levels through Western blotting and determine the relative expression levels of ACAN, IL-1β, IL-6, and TNF-α through qPCR. All affected animals presented chondrodysplasia-like lesions with disorganization of the chondrocyte layers and reduced the amount of an extracellular matrix. No significant difference in aggrecan expression levels in uncleaved samples from the dwarf and control groups (composed of phenotypically normal animals of similar age and breed (P = .7143)) was found using Western blotting. qPCR revealed that ACAN gene expression was higher in the affected animals than in normal animals (P = .0119). No significant difference in cytokine levels was detected between the groups. Mutant aggrecan may interfere with normal cellular function, leading to chondrodysplasia and the observed phenotypic findings.
Publication Date: 2021-04-30 PubMed ID: 34281639DOI: 10.1016/j.jevs.2021.103643Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research examines the expression of a specific protein (aggrecan) and certain cytokines in the joint cartilage of Miniature horses with a dwarfism disorder. The results provide insight into the cellular mechanisms of this form of dwarfism, suggesting that mutated aggrecan may disrupt cell functions and cause the dwarfism symptoms.

Objective of the Study

  • The researchers aimed to investigate the expression of aggrecan, both at the gene and protein level, and the cytokines IL-1β, IL-6, and TNF-α, all found in joint cartilage of miniature horses with chondrodysplastic dwarfism.

Methodology

  • They collected metatarsal bone and joint cartilage samples from eight miniature horses with the dwarfish disorder. The gene and protein expression of aggrecan, and the relative expression levels of the cytokines IL-1β, IL-6, and TNF-α, were evaluated using Western blot tests and qPCR.
  • The findings from the dwarf horses were compared with similar age and breed category of normal horses (control groups) to note any significant differences.

Results

  • All dwarf horses examined presented disorganized chondrocyte layers and reduced extracellular matrix, both of which are characteristics of chondrodysplasia.
  • No significant variation in the expression of aggrecan protein in the dwarf and control groups was noticed when inspected via the Western blot test.
  • However, higher aggrecan gene expression was found in the dwarf horses when compared to the normal counterparts through qPCR.
  • Moreover, no significant differences in cytokine levels were observed between the dwarf and normal groups.

Interpretation and Conclusion

  • The researchers suggest that despite the similar levels of aggrecan protein, the mutant aggrecan gene could interfere with normal cell functions, leading to abnormalities in cartilage structure – an indicator of chondrodysplasia.

Cite This Article

APA
Basso RM, Andrade DGA, Alves CEF, Laufer-Amorim R, Borges AS, Oliveira-Filho JP. (2021). Aggrecan, IL-1β, IL-6, and TNF-α profiles in the Articular Cartilage of Miniature Horses with Chondrodysplastic Dwarfism. J Equine Vet Sci, 103, 103643. https://doi.org/10.1016/j.jevs.2021.103643

Publication

ISSN: 0737-0806
NlmUniqueID: 8216840
Country: United States
Language: English
Volume: 103
Pages: 103643
PII: S0737-0806(21)00273-2

Researcher Affiliations

Basso, Roberta M
  • São Paulo State University (UNESP), School of Veterinary Medicine and Animal Science, Department of Veterinary Clinical Science, Botucatu 18618-681, Brazil.
Andrade, Danilo G A
  • São Paulo State University (UNESP), School of Veterinary Medicine and Animal Science, Department of Veterinary Clinical Science, Botucatu 18618-681, Brazil.
Alves, Carlos E F
  • São Paulo State University (UNESP), School of Veterinary Medicine and Animal Science, Department of Veterinary Clinical Science, Botucatu 18618-681, Brazil.
Laufer-Amorim, Renée
  • São Paulo State University (UNESP), School of Veterinary Medicine and Animal Science, Department of Veterinary Clinical Science, Botucatu 18618-681, Brazil.
Borges, Alexandre S
  • São Paulo State University (UNESP), School of Veterinary Medicine and Animal Science, Department of Veterinary Clinical Science, Botucatu 18618-681, Brazil.
Oliveira-Filho, Jose P
  • São Paulo State University (UNESP), School of Veterinary Medicine and Animal Science, Department of Veterinary Clinical Science, Botucatu 18618-681, Brazil. Electronic address: jose.oliveira-filho@unesp.br.

MeSH Terms

  • Aggrecans / genetics
  • Animals
  • Cartilage, Articular
  • Dwarfism / genetics
  • Dwarfism / veterinary
  • Horse Diseases / genetics
  • Horses
  • Interleukin-6 / genetics
  • Tumor Necrosis Factor-alpha / genetics

Citations

This article has been cited 1 times.
  1. Wu B, Guo X, Yan X, Tian Z, Jiang W, He X. TSG-6 inhibits IL-1β-induced inflammatory responses and extracellular matrix degradation in nucleus pulposus cells by activating the PI3K/Akt signaling pathway.. J Orthop Surg Res 2022 Dec 28;17(1):572.
    doi: 10.1186/s13018-022-03468-9pubmed: 36578051google scholar: lookup