Regulation of Sox9 activity by crosstalk with nuclear factor-kappaB and retinoic acid receptors

Arthritis Research & Therapy
Jason S RockelSuzanne M Bernier

Abstract

Sox9 and p300 cooperate to induce expression of cartilage-specific matrix proteins, including type II collagen, aggrecan and link protein. Tumour necrosis factor (TNF)-alpha, found in arthritic joints, activates nuclear factor-kappaB (NF-kappaB), whereas retinoic acid receptors (RARs) are activated by retinoid agonists, including all-trans retinoic acid (atRA). Like Sox9, the activity of NF-kappaB and RARs depends upon their association with p300. Separately, both TNF-alpha and atRA suppress cartilage matrix gene expression. We investigated how TNF-alpha and atRA alter the expression of cartilage matrix genes. Primary cultures of rat chondrocytes were treated with TNF-alpha and/or atRA for 24 hours. Levels of transcripts encoding cartilage matrix proteins were determined by Northern blot analyses and quantitative real-time PCR. Nuclear protein levels, DNA binding and functional activity of transcription factors were assessed by immunoblotting, electrophoretic mobility shift assays and reporter assays, respectively. Together, TNF-alpha and atRA diminished transcript levels of cartilage matrix proteins and Sox9 activity more than each factor alone. However, neither agent altered nuclear levels of Sox9, and TNF-alpha did not affec...Continue Reading

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Citations

Jun 10, 2009·Matrix Biology : Journal of the International Society for Matrix Biology·Jason S RockelAndrew Leask
Feb 17, 2015·Genes & Diseases·Alice JoRex C Haydon
Nov 1, 2015·Biochemical Society Transactions·Andrew D Rowan, Gary J Litherland
Jun 23, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Venkata Krishnaraju AlluriEswar Kumar Kilari
Apr 3, 2020·International Journal of Molecular Sciences·Tsuyoshi ShimoMasahiro Iwamoto
Sep 14, 2012·Annals of Thoracic and Cardiovascular Surgery : Official Journal of the Association of Thoracic and Cardiovascular Surgeons of Asia·Jianmei JinZhidong Guo

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Methods Mentioned

BETA
PCR
transfection
Assay
electrophoretic mobility shift
electrophoresis
nuclear translocation
acetylation

Software Mentioned

PRISM
Kodak Digital Science
GraphPad
SDS

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