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Home / Equine Research Bank / Osteoarthritis Cartilage / Regulation of SOX9 in normal and osteoarthritic equine artic...
Osteoarthritis and cartilage2010; 18(11); 1502-1508; doi: 10.1016/j.joca.2010.08.011

Regulation of SOX9 in normal and osteoarthritic equine articular chondrocytes by hyperosmotic loading.

Abstract: SOX9 is a transcription factor that is essential for cartilage extracellular matrix (ECM) formation. Osteoarthritis (OA) is characterised by a loss of cartilage ECM. In chondrocytes SOX9 gene expression is regulated by osmotic loading. Here we characterise SOX9 mRNA regulation through static and cyclical application of hyperosmotic conditions in normal and OA monolayer equine chondrocytes. Furthermore, we investigate whether extracellular signal-regulated protein kinase (ERK)1/2 mitogen-activated protein kinases (MAPK) pathways have a role in this regulation of SOX9. Methods: Equine chondrocytes harvested from normal or OA joints were subjected to different osmotic loading patterns as either primary (P0) or passaged (P2) cells. The involvement of MEK-ERK signalling was demonstrated by using pharmacological inhibitors. In addition SOX9 gene stability was determined. Levels of transcripts encoding SOX9, Col2A1 and aggrecan were measured using qRT-PCR. De novo glycosaminoglycan synthesis of explants was determined with (35)S sulphate during static hyperosmolar loading. Results: MEK-ERK signalling increases glycosaminoglycans (GAG) synthesis in explants. Static hyperosmotic conditions significantly reduced SOX9 mRNA in normal P2 and OA P0 but not normal P0 chondrocytes. SOX9 mRNA was stabilised by hyperosmotic conditions. Cyclical loading of normal P2 and OA P0 but not normal P0 cells led to an increase in SOX9 gene expression and this was prevented by MEK1/2 inhibition. Conclusions: The response to osmotic loading of SOX9 mRNA is dependent on the nature of the osmotic stimulation and the chondrocyte phenotype. This variation may be important in disease progression.
Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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Publication Date: 2010-08-26 PubMed ID: 20800688PubMed Central: PMC3078327DOI: 10.1016/j.joca.2010.08.011Google Scholar: Lookup
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  • Journal Article
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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 investigates how osmotic loading, or changes in the concentration of a solution, affects the regulation of an essential gene known as SOX9 in normal and osteoarthritic horse articular chondrocytes, or cartilage cells. The study also explores how a signaling pathway called ERK1/2 MAPK impacts this regulation.

Research Methodology

  • The research process involved subjecting equine chondrocytes (cartilage cells), harvested from both normal and osteoarthritis (OA) affected joints, to different osmotic loading patterns. These cells were either primary (P0) or passaged (P2) cells.
  • The research evaluated the involvement of the MEK-ERK signaling pathway in this process through the use of pharmacological inhibitors.
  • Furthermore, the research measured the levels of transcripts encoding SOX9, Col2A1, and aggrecan using a technique called qRT-PCR.
  • Determination of new glycosaminoglycan synthesis of explants was performed using (35)S sulphate during static hyperosmolar loading conditions.

Findings

  • The study found that MEK-ERK signaling increases the synthesis of glycosaminoglycans in explants. Glycosaminoglycans are large molecules that serve as the main building block of cartilage tissue, attracting and holding on to water to lubricate and cushion the joints.
  • Static hyperosmotic conditions (conditions of high osmotic pressure) significantly reduced SOX9 mRNA in normal P2 and OA P0 but not normal P0 chondrocytes. This indicates that osmotic stress can suppress the critical SOX9 gene expression associated with cartilage formation.
  • Contrarily, the study discovered that SOX9 mRNA was stabilized by hyperosmotic conditions.
  • Subjecting normal P2 and OA P0, but not normal P0 cells, to cyclical loading led to increased SOX9 gene expression. However, MEK1/2 inhibition prevented this rise, highlighting the intricate role of the MEK-ERK signaling in this process.

Conclusions

  • The study concludes that the response of SOX9 mRNA to osmotic loading greatly depends on the nature of the osmotic stimulation and the state of the chondrocyte, whether it’s a normal or OA cell.
  • The variable response to osmotic loading could be vital in the progression and understanding of degenerative ailments like osteoarthritis—characterized by a loss of cartilage extracellular matrix (ECM).

Cite This Article

APA
Peffers MJ, Milner PI, Tew SR, Clegg PD. (2010). Regulation of SOX9 in normal and osteoarthritic equine articular chondrocytes by hyperosmotic loading. Osteoarthritis Cartilage, 18(11), 1502-1508. https://doi.org/10.1016/j.joca.2010.08.011

Publication

Osteoarthritis and cartilage
ISSN: 1522-9653
NlmUniqueID: 9305697
Country: England
Language: English
Volume: 18
Issue: 11
Pages: 1502-1508

Researcher Affiliations

Peffers, M J
  • Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Leahurst, Neston, Wirral , CH64 7TE, UK. peffs@liverpool.ac.uk
Milner, P I
    Tew, S R
      Clegg, P D

        MeSH Terms

        • Aggrecans / metabolism
        • Animals
        • Cartilage, Articular / metabolism
        • Chondrocytes / metabolism
        • Gene Expression Regulation
        • Glycosaminoglycans / metabolism
        • Horses
        • Osmolar Concentration
        • Osteoarthritis / metabolism
        • RNA, Messenger / metabolism
        • Reverse Transcriptase Polymerase Chain Reaction
        • SOX9 Transcription Factor / genetics
        • SOX9 Transcription Factor / metabolism
        • Sequence Analysis, DNA

        Grant Funding

        • WT085324MA / Wellcome Trust
        • Arthritis Research UK

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