TY - JOUR
T1 - Gene expression and functional comparison between multipotential stromal cells from lateral and medial condyles of knee osteoarthritis patients
AU - Sanjurjo-Rodriguez, Clara
AU - Baboolal, Thomas G.
AU - Burska, Agata N.
AU - Ponchel, Frederique
AU - El-Jawhari, Jehan J.
AU - Pandit, Hemant
AU - McGonagle, Dennis
AU - Jones, Elena
N1 - Funding Information:
C. Sanjurjo-Rodriguez is beneficiary of a postdoctoral fellowship from Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria). T Baboolal and D McGonagle are part-supported by the National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. T Baboolal is also part-supported by FOREUM: foundation for research in rheumatology grant number 104929. J El-Jawhari is part-funded by AO foundation start-up grant (grant number S-16-132E). We gratefully acknowledge Mike Shires, Adam Davison and Liz Straszynski for research support services at the Leeds Institute of Rheumatic and Musculoskeletal Medicine, and patients and staff of Chapel Allerton Orthopaedic Centre.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-019-45820-w
DO - 10.1038/s41598-019-45820-w
M3 - Article
C2 - 31249374
AN - SCOPUS:85068087804
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 9321
ER -