Gene expression and functional comparison between multipotential stromal cells from lateral and medial condyles of knee osteoarthritis patients

Thomas G Baboolal,Clara Sanjurjo-Rodriguez,Elena Jones,Hemant Pandit,Dennis Mcgonagle,Agata N Burska,Frederique Ponchel,Jehan J El-Jawhari

doi:10.1038/s41598-019-45820-w

Abstract

Osteoarthritis (OA) is the most common degenerative joint disorder. Multipotential stromal cells (MSCs) have a crucial role in joint repair, but how OA severity affects their characteristics remains unknown. Knee OA provides a good model to study this, as osteochondral damage is commonly more severe in the medial weight-bearing compartment compared to lateral side of the joint. This study utilised in vitro functional assays, cell sorting, gene expression and immunohistochemistry to compare MSCs from medial and lateral OA femoral condyles. Despite greater cartilage loss and bone sclerosis in medial condyles, there was no significant differences in MSC numbers, growth rates or surface phenotype. Culture-expanded and freshly-purified medial-condyle MSCs expressed higher levels of several ossification-related genes. Using CD271-staining to identify MSCs, their presence and co-localisation with TRAP-positive chondroclasts was noted in the vascular channels breaching the osteochondral junction in lateral condyles. In medial condyles, MSCs were additionally found in small cavities within the sclerotic plate. These data indicate subchondral MSCs may be involved in OA progression by participating in cartilage destruction, calcification and sclerotic plate formation and that they remain abundant in severe disease. Biological or biomechanical modulation of these MSCs may be a new strategy towards cartilage and bone restoration in knee OA.

Highlights

Osteoarthritis (OA) is the major cause of chronic pain and disability and its incidence is predicted to increase in coming decades[1,2]
Four out of five medial condyles had OARSI score of 20 indicating maximum damage characterized by denuded bone in more than 50% of the specimen surface
This study evaluated numerical, topographical and gene expression changes in subchondral bone Multipotential stromal cells (MSCs) in knee OA, in relation to osteochondral damage progression, by comparing the medial and lateral femoral condyles from the same patients with varus deformity knee OA

Summary

Introduction

Osteoarthritis (OA) is the major cause of chronic pain and disability and its incidence is predicted to increase in coming decades[1,2]. We have previously shown the presence of MSCs in healthy and arthritic SF, and their numerical increase in OA compared to arthroscopically normal joints[10] Despite their apparent increase as the disease progresses[13], cartilage lesions in OA continue to deteriorate suggesting that locally available SF MSCs have reduced joint repair potentials, possibly due to their impaired attachment to cartilage[14], reduced chondrogenic ability[15] or persistent abnormal joint mechanical loading[4]. We hypothesised that due to increased molecular exchanges through damaged osteochondral junction, parallel gene expression alterations can be seen in medial condyle chondrocytes. As gene expression in bone-resident MSCs is known to be affected by culture expansion[22,23,24], the analysis was performed on MSCs directly taken from their native environment as well as following culture expansion

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