Abstract

Fibrillin-1 expression, which regulates of TGF-B bioavailability, is modified during osteoarthritis and mutations lead to osteoarthritis

Highlights

  • The TGFb signalling pathway has been shown to play a major role in joint homeostasis and in osteoarthritis development

  • Our library of epigenetic modifying compounds includes those targeting methyltrasnferases, histone deacetylases, histone protein kinases and bromodomains. In this preliminary work we have screened this library for impact on cell phenotype in chondrogenesis and in primary human articular chondrocytes (HAC) Methods: Primary human articular chondrocytes (HAC) and human mesencymal stem cells (MSCs) undergoing chondrogenesis were treated with epigenetic modifying compounds for 72 hours

  • HAC were treated with GSK-J4 and GSK-J5 for 6h and TIMP3 and COL2A1 expression assessed by qPCR

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Summary

Introduction

The TGFb signalling pathway has been shown to play a major role in joint homeostasis and in osteoarthritis development. Results: In this study, we found that the absence of locally produced Bmp7 reduced proteoglycan contents in articular cartilage matrix in the adult mice (at 8 and 24 weeks of age). This may not be due to the defect in cartilage formation since there was no significant alteration in both articular structure and proteoglycan contents in the juvenile :7CKO mice (at 4 weeks of age).

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