Deletion of Dual Specificity Phosphatase 1 Does Not Predispose Mice to Increased Spontaneous Osteoarthritis.

Michael Andrew Pest,Frank Beier,Courtney Alice Pest,Melina Rodrigues Bellini,Qingping Feng

doi:10.1371/journal.pone.0142822

Michael Andrew Pest, Frank Beier + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0142822

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Journal: PloS one	Publication Date: Nov 12, 2015
Citations: 50	License type: CC BY 4.0

Affiliation: Western University

Abstract

BackgroundOsteoarthritis (OA) is a degenerative joint disease with poorly understood etiology and pathobiology. Mitogen activated protein kinases (MAPKs) including ERK and p38 play important roles in the mediation of downstream pathways involved in cartilage degenerative processes. Dual specificity phosphatase 1 (DUSP1) dephosphorylates the threonine/serine and tyrosine sites on ERK and p38, causing deactivation of downstream signalling. In this study we examined the role of DUSP1 in spontaneous OA development at 21 months of age using a genetically modified mouse model deficient in Dusp1 (DUSP1 knockout mouse).ResultsUtilizing histochemical stains of paraffin embedded knee joint sections in DUSP1 knockout and wild type female and male mice, we showed similar structural progression of cartilage degeneration associated with OA at 21 months of age. A semi-quantitative cartilage degeneration scoring system also demonstrated similar scores in the various aspects of the knee joint articular cartilage in DUSP1 knockout and control mice. Examination of overall articular cartilage thickness in the knee joint demonstrated similar results between DUSP1 knockout and wild type mice. Immunostaining for cartilage neoepitopes DIPEN, TEGE and C1,2C was similar in the cartilage lesion sites and chondrocyte pericellular matrix of both experimental groups. Likewise, immunostaining for phosphoERK and MMP13 showed similar intensity and localization between groups. SOX9 immunostaining demonstrated a decreased number of positive cells in DUSP1 knockout mice, with correspondingly decreased staining intensity. Analysis of animal walking patterns (gait) did not show a discernable difference between groups.ConclusionLoss of DUSP1 does not cause changes in cartilage degeneration and gait in a mouse model of spontaneous OA at 21 months of age. Altered staining was observed in SOX9 immunostaining which may prove promising for future studies examining the role of DUSPs in cartilage and OA, as well as models of post-traumatic OA.

Highlights

Osteoarthritis (OA) is a degenerative joint disease which is estimated to afflict at least 10% of the US population over the age of 25 [1]
Utilizing histochemical stains of paraffin embedded knee joint sections in Dual specificity phosphatase 1 (DUSP1) knockout and wild type female and male mice, we showed similar structural progression of cartilage degeneration associated with OA at 21 months of age
Immunostaining for cartilage neoepitopes DIPEN, TEGE and C1,2C was similar in the cartilage lesion sites and chondrocyte pericellular matrix of both experimental groups

Summary

Introduction

Osteoarthritis (OA) is a degenerative joint disease which is estimated to afflict at least 10% of the US population over the age of 25 [1]. Symptoms of OA include joint pain and stiffness which can become severe enough to limit activity and ability to work. Chondrocytes are the only active cellular component of the cartilage that caps the bone in articular joints such as the knee, elbow and ankle. These cells maintain tissue homeostasis by balancing anabolic buildup and catabolic turnover of surrounding extracellular matrix (ECM) proteins [2]. An imbalance in ECM turnover, and tissue homeostasis is thought to be one of the primary underlying reasons for cartilage degeneration in OA This imbalance is largely driven by certain growth factors and inflammatory cytokine signalling [2]

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