Gene Expression Signatures of Synovial Fluid Multipotent Stromal Cells in Advanced Knee Osteoarthritis and Following Knee Joint Distraction
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Gene Expression Signatures of Synovial Fluid Multipotent Stromal Cells in Advanced Knee Osteoarthritis and Following Knee Joint DistractionAutor(es)
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2020-10-14Cita bibliográfica
Sanjurjo-Rodriguez C, Altaie A, Mastbergen S, et al. Gene Expression Signatures of Synovial Fluid Multipotent Stromal Cells in Advanced Knee Osteoarthritis and Following Knee Joint Distraction. Front. Bioeng. Biotechnol. 2020; 8:579751
Resumo
[Abstract]
Osteoarthritis (OA) is the most common musculoskeletal disorder. Although joint
replacement remains the standard of care for knee OA patients, knee joint distraction
(KJD), which works by temporarily off-loading the joint for 6–8 weeks, is becoming
a novel joint-sparing alternative for younger OA sufferers. The biological mechanisms
behind KJD structural improvements remain poorly understood but likely involve jointresident regenerative cells including multipotent stromal cells (MSCs). In this study,
we hypothesized that KJD leads to beneficial cartilage-anabolic and anti-catabolic
changes in joint-resident MSCs and investigated gene expression profiles of synovial
fluid (SF) MSCs following KJD as compared with baseline. To obtain further insights
into the effects of local biomechanics on MSCs present in late OA joints, SF MSC
gene expression was studied in a separate OA arthroplasty cohort and compared with
subchondral bone (SB) MSCs from medial (more loaded) and lateral (less loaded) femoral
condyles from the same joints. In OA arthroplasty cohort (n = 12 patients), SF MSCs
expressed lower levels of ossification- and hypotrophy-related genes [bone sialoprotein
(IBSP), parathyroid hormone 1 receptor (PTH1R), and runt-related transcription factor
2 (RUNX2)] than did SB MSCs. Interestingly, SF MSCs expressed 5- to 50-fold
higher levels of transcripts for classical extracellular matrix turnover molecules matrix
metalloproteinase 1 (MMP1), a disintegrin and metalloproteinase with thrombospondin
motifs 5 (ADAMTS5), and tissue inhibitor of metalloproteinase-3 (TIMP3), all (p < 0.05)
potentially indicating greater cartilage remodeling ability of OA SF MSCs, compared
with SB MSCs. In KJD cohort (n = 9 patients), joint off-loading resulted in sustained,
significant increase in SF MSC colonies’ sizes and densities and a notable transcript
upregulation of key cartilage core protein aggrecan (ACAN) (weeks 3 and 6), as well
as reduction in pro-inflammatory C–C motif chemokine ligand 2 (CCL2) expression (weeks 3 and 6). Additionally, early KJD changes (week 3) were marked by significant
increases in MSC chondrogenic commitment markers gremlin 1 (GREM1) and growth
differentiation factor 5 (GDF5). In combination, our results reveal distinct transcriptomes
on joint-resident MSCs from different biomechanical environments and show that 6-
week joint off-loading leads to transcriptional changes in SF MSCs that may be beneficial
for cartilage regeneration. Biomechanical factors should be certainly considered in the
development of novel MSC-based therapies for OA.
Palabras chave
Multipotent stromal cells
Synovial fluid
Osteoarthritis
Knee joint distraction
Subchondral bone
Chondrocytes
Synovial fluid
Osteoarthritis
Knee joint distraction
Subchondral bone
Chondrocytes
Versión do editor
Dereitos
Atribución 4.0 España
ISSN
2296-4185