Insights into Osteoarthritis Progression by Gene Expression and miRNA Profiling of Mesenchymal Stromal Cells from Medial and Lateral Femoral Condyles

Clara Sanjurjo-Rodríguez ¹, Rachel Crossland ², Thomas Baboolal ³, Monica Reis ⁴, Agata Burska ⁵, Frederique Ponchel ⁵, Jehan El-Jawhari ⁵, Dennis McGonagle⁶, Hemant Pandit ⁷, Xiao-nong Wang ⁸ and Elena Jones ⁹, ¹Grupo de investigación en Terapia Celular y Medicina Regenerativa. Departamento de Fisioterapia, Medicina y Ciencias Biomédicas. Universidade da Coruña. Agrupación estratégica CICA-INIBIC. A Coruña, España; University of Leeds; Newcastle University, A Coruña, Spain, ²2Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom, ³Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM)University of Leeds, Leeds, United Kingdom, ⁴Department of Pediatrics, Harvard Medical School, Boston, MA, USA, Boston, ⁵Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom, ⁶University of Leeds, Leeds, United Kingdom, ⁷Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds. NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, ⁸Institute of Cellular Medicine, Newcastle University, UK, Newcastle, United Kingdom, ⁹University of Leeds, Leeds, England, United Kingdom

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: MSCs and ev, OA

Session Information

Date: Tuesday, November 12, 2019

Title: Osteoarthritis & Joint Biology – Basic Science Poster

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Bone marrow multipotential stromal cells (MSC) are widely used in clinical trials to treat bone and cartilage diseases. However, there is limited information on the role of MSC in the pathogenesis in humans. As osteoarthritis (OA) severity is often associated with an abnormal movement and load distribution on the medial compartment of the knee, the aim of this study was to determine differences in MSC topography and gene expression between the diseased medial and more “macroscopically normal” lateral femoral condyles. Also, we investigated the miRNA profiling of cargo from extracellular vesicles (EVs) secreted by medial OA MSCs (OAMSC-EVs) compared with the ones secreted by healthy MSCs (HMSC-EVs).

Methods: OA MSCs were obtained from femoral condyles of total knee replacement patients and were extracted from subchondral bone after digestion and sorted using the CD271+CD45- phenotype for gene expression analysis. MSCs from healthy donors were isolated from bone marrow aspirate by density gradient centrifugation using Lymphoprep and culture expanded for EV isolation. EVs were isolated from medial and healthy MSCs by differential centrifugation and characterized before miRNA profiling using NanoString technology.

Results: Medial condyles presented higher degree of cartilage damage (OARSI score 20) compared to lateral condyles (OARSI score 3) and sclerotic subchondral bone area was higher in the medial condyles (64.3±7.0% vs 27.6±7.4% area in lateral condyles). CD271+ cells in medial and lateral femoral condyles did not show differences in topography or numbers, and cultured MSCs also presented similar growth rates and trilineage capacities in vitro. Three genes were significantly upregulated in medial condyle CD271+ MSCs: GREM1 (lateral MSCs below detection), PTHLH (2.4-fold, p=0.02) and STMN2 (10.5-fold, p=0.02), all of them implicated in osteogenic differentiation and mineralisation. miRNA profiling showed 46 miRNA differentially expressed between OAMSC-EVs and HMSC-EVs.

Conclusion: Despite the apparent differences in cartilage damage and bone sclerosis, no major differences were found between medial and lateral condyles. However, there was upregulation of genes implicated in osteogenic differentiation and mineralisation in medial condyle MSCs that can be associated with sclerotic-plate formation. Also, there was differences in miRNA between medial and healthy MSCs and MSC-EVs, for which the target genes and implicated pathways need further investigation.

Disclosure: C. Sanjurjo-Rodríguez, None; R. Crossland, None; T. Baboolal, None; M. Reis, None; A. Burska, None; F. Ponchel, None; J. El-Jawhari, None; D. McGonagle, AbbVie, 9, Abbvie, 2, 8, BMS, 9, Celgene, 2, 8, 9, Janssen, 2, 8, Johnson & Johnson, 9, Lilly, 2, 8, MSD, 9, Novartis, 2, 8, 9, Pfizer, 2, 8, 9, UCB, 8, 9; H. Pandit, None; X. Wang, None; E. Jones, None.

To cite this abstract in AMA style:

Sanjurjo-Rodríguez C, Crossland R, Baboolal T, Reis M, Burska A, Ponchel F, El-Jawhari J, McGonagle D, Pandit H, Wang X, Jones E. Insights into Osteoarthritis Progression by Gene Expression and miRNA Profiling of Mesenchymal Stromal Cells from Medial and Lateral Femoral Condyles [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/insights-into-osteoarthritis-progression-by-gene-expression-and-mirna-profiling-of-mesenchymal-stromal-cells-from-medial-and-lateral-femoral-condyles/. Accessed .

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