Objectives: Decreased levels of transforming growth factor beta (TGFβ) have been related to the failure of cartilage repair in experimental models of osteoarthritis. This study aimed to examine this aspect of osteoarthritis in human cartilage.
Methods: Cartilage samples were obtained from 11 patients with hip osteoarthritis and 11 patients with femoral neck fracture who were undergoing total hip replacement. Gene expression of the three TGFβ isoforms, collagen type II (COL2A1) and aggrecan (AGC1) was analysed by reverse transcription quantitative PCR and immunohistochemistry.
Results: Expression of the three TGFβ isoforms was increased in osteoarthritis cartilage. The upregulation was more marked for the TGFβ3 isoform (2.3-fold) than for TGFβ1 (1.6-fold) or TGFβ2 (1.7-fold). The messenger RNA levels of TGFβ1 and TGFβ2 were strongly correlated in osteoarthritis cartilage (rs = 0.83, p = 0.002), but levels of TGFβ3 were uncorrelated with any of the two other TGFβ isoforms. Immunohistochemistry showed an extension of immunoreactivity for the three TGFβ isoforms to more chondrocytes and to deeper cartilage layers in the more severe osteoarthritis lesions. No correlation of TGFβ isoforms with COL2A1 or AGC1 expression levels was found.
Conclusions: The three isoforms of TGFβ were differentially upregulated in late osteoarthritis in relation to an increased percentage of TGFβ-positive chondrocytes. These results indicate that cartilage damage progresses in spite of the TGFβ stimulus for cartilage anabolism and that other causes of the failure to cope with the increased cartilage catabolism of osteoarthritis should be investigated.
Statistics from Altmetric.com
Competing interests: None.
Funding: This project was financed by the MMA Foundation (Madrid, Spain). MP-S received a bursary from the Fundacion Española de Reumatologia (Madrid) and a post-MIR contract from the Instituto de Salud Carlos III (Madrid).
Ethics approval: This study was approved by the ethical committee for clinical research of Galicia.
Patient consent: Obtained.
▸ Additional tables and figures are published online only at http://ard.bmj.com/content/vol68/issue4
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.