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Identification of novel osteochondrosis–Associated genes.

Abstract: During the early stages of articular osteochondrosis, cartilage is retained in subchondral bone, but the pathophysiology of this condition of growing humans and domestic animals is poorly understood. A subtractive hybridization study was undertaken to compare gene expression between the cartilage of early experimentally induced equine osteochondrosis lesions and control cartilage. Of the many putative differentially expressed genes identified, eight were confirmed by quantitative PCR analysis as differentially expressed, in addition to those already known to be associated with early lesions. Genes encoding vacuolar H(+)-ATPase V0 subunit d2 (ATP6V0D2), cathepsin K, integrin-binding sialoprotein, integrin αV, low density lipoprotein receptor-related protein 4, lumican, osteopontin, and thymosin β4 (TMSB4) were expressed at higher levels in lesions than in control cartilage. These genes included 34 genes not previously identified in cartilage. Some genes identified as associated with early lesions are known chondrocyte hypertrophy-associated genes, and in transmission electron microscopy studies normal hypertrophic chondrocytes were observed in lesions. Differential expression of ATP6V0D2 and TMSB4 in the cartilage of early naturally occurring osteochondrosis lesions was confirmed by immunohistochemistry. These results identify novel osteochondrosis-associated genes and provide evidence that articular osteochondrosis does not necessarily result from failure of chondrocytes to undergo hypertrophy.
Publication Date: 2015-09-08 PubMed ID: 26296056DOI: 10.1002/jor.23033Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This study has revealed eight new genes that show differing levels of activity in horses with early-stage osteochondrosis, a condition where cartilage does not adequately convert to bone, in comparison to healthy controls. This opens up potential new areas of study in understanding and treating this condition in both humans and animals.

Identification of Novel Osteochondrosis-Associated Genes

  • The researchers undertook a study based on subtractive hybridization to observe the gene expression difference between cartilage affected by early-stage osteochondrosis and healthy control cartilage.
  • Several genes were discovered to be expressed at varying levels in the diseased versus healthy cartilage. Those significantly more active in the osteochondrosis-affected tissue included genes encoding for ATP6V0D2, cathepsin K, integrin-binding sialoprotein, integrin αV, low-density lipoprotein receptor-related protein 4, lumican, osteopontin, and TMSB4.
  • These include 34 genes not previously identified in cartilage, representing several new avenues of potential research into the genetic aspect of osteochondrosis.

Chondrocyte Behavior in Osteochondrosis

  • Some of the genes associated with early osteochondrosis are known to be linked with chondrocyte hypertrophy indicating that the chondrocytes – the cartilage producing cells – might be behaving differently or are influenced differently in the early stages of osteochondrosis.
  • Under the electron microscope, the researchers noted the presence of normal hypertrophic chondrocytes in lesions, suggesting that the process of cartilage transforming to bone – which is the normal function of chondrocytes – might still be taking place, debunking some previous theories about the pathophysiology of osteochondrosis.

Confirmation of Findings

  • Differential expression of ATP6V0D2 and TMSB4 in early naturally occurring osteochondrosis lesions was also confirmed by a different technique, immunohistochemistry.
  • This suggests that the findings from the initial gene expression study are accurate and hold true in naturally-occurring cases of osteochondrosis, not just in experimentally induced ones.

In conclusion, this study has identified a number of new genes related to osteochondrosis and shed some light on the previously poorly-understood condition in which chondrocytes do not adequately transform cartilage to bone. It opens up the possibility of future research and interventions that could improve the pathophysiology or treatment of osteochondrosis.

Cite This Article

APA
Mirams M, Ayodele BA, Tatarczuch L, Henson FM, Pagel CN, Mackie EJ. (2015). Identification of novel osteochondrosis–Associated genes. J Orthop Res, 34(3), 404-411. https://doi.org/10.1002/jor.23033

Publication

ISSN: 1554-527X
NlmUniqueID: 8404726
Country: United States
Language: English
Volume: 34
Issue: 3
Pages: 404-411

Researcher Affiliations

Mirams, Michiko
  • Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
Ayodele, Babatunde A
  • Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
Tatarczuch, Liliana
  • Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
Henson, Frances M
  • Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
Pagel, Charles N
  • Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
Mackie, Eleanor J
  • Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, VIC 3010, Australia.

MeSH Terms

  • Animals
  • Chondrocytes / pathology
  • Gene Expression Profiling
  • Horses
  • Hypertrophy
  • Osteochondrosis / genetics
  • Osteochondrosis / metabolism
  • Osteochondrosis / pathology
  • Vacuolar Proton-Translocating ATPases / metabolism

Citations

This article has been cited 8 times.
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