The retinoic acid binding protein CRABP2 is increased in murine models of degenerative joint diseaseReport as inadecuate




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Arthritis Research and Therapy

, 11:R14

First Online: 28 January 2009Received: 12 September 2008Revised: 04 December 2008Accepted: 28 January 2009

Abstract

IntroductionOsteoarthritis OA is a debilitating disease with poorly defined aetiology. Multiple signals are involved in directing the formation of cartilage during development and the vitamin A derivatives, the retinoids, figure prominently in embryonic cartilage formation. In the present study, we examined the expression of a retinoid-regulated gene in murine models of OA.

MethodsMild and moderate forms of an OA-like degenerative disease were created in the mouse stifle joint by meniscotibial transection MTX and partial meniscectomy PMX, respectively. Joint histopathology was scored using an Osteoarthritis Research Society International OARSI system and gene expression Col1a1, Col10a1, Sox9 and Crabp2 in individual joints was determined using TaqMan quantitative PCR on RNA from microdissected articular knee cartilage.

ResultsFor MTX, there was a significant increase in the joint score at 10 weeks n = 4, p < 0.001 in comparison to sham surgeries. PMX surgery was slightly more severe and produced significant changes in joint score at six n = 4, p < 0.01, eight n = 4, p < 0.001 and 10 n = 4, p < 0.001 weeks. The expression of Col1a1 was increased in both surgical models at two, four and six weeks post-surgery. In contrast, Col10a1 and Sox9 for the most part showed no significant difference in expression from two to six weeks post-surgery. Crabp2 expression is induced upon activation of the retinoid signalling pathway. At two weeks after surgery in the MTX and PMX animals, Crabp2 expression was increased about 18-fold and about 10-fold over the sham control, respectively. By 10 weeks, Crabp2 expression was increased about three-fold n = 7, not significant in the MTX animals and about five-fold n = 7, p < 0.05 in the PMX animals in comparison to the contralateral control joint.

ConclusionsTogether, these findings suggest that the retinoid signalling pathway is activated early in the osteoarthritic process and is sustained during the course of the disease.

AbbreviationsACANaggrecan

ACLanterior cruciate ligament

ANOVAanalysis of variance

DMMdestabilisation of the medial meniscus

DJDdegenerative joint disease

ECMextracellular matrix

MCLmedial collateral ligament

MTXmeniscotibial transection

OAosteoarthritis

PMXpartial meniscoectomy

RT-qPCRreverse transcription quantitative polymerase chain reaction.

Electronic supplementary materialThe online version of this article doi:10.1186-ar2604 contains supplementary material, which is available to authorized users.

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Author: Ian D Welch - Matthew F Cowan - Frank Beier - Tully M Underhill

Source: https://link.springer.com/







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