title: Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis.
abstract: In patients with osteoarthritis (OA), bone marrow lesions (BMLs) are intimately linked to disease progression. We hypothesized that aberrant multipotential stromal cell (also known as mesenchymal stem cell [MSC]) responses within bone tissue contributes to BML pathophysiology. The aim of this study was to investigate BML and non-BML native subchondral bone MSCs for numeric, topographic, in vitro functional, and gene expression differences.
  
  
  
  Ex vivo 3T magnetic resonance imaging (MRI) of the femoral heads of 20 patients with hip OA was performed. MRI-determined BML and non-BML regions were excised and enzymatically treated to extract cells and quantify MSCs using flow cytometry and colony-forming unit-fibroblast (CFU-F) assay. Immunohistochemical analysis was performed to determine in vivo CD271+ MSC distribution. Culture-expanded CD271+ cells were analyzed for tripotentiality and gene expression.
  
  
  
  BML regions were associated with greater trabecular bone area and cartilage damage compared with non-BML regions. The proportion of CD45-CD271+ MSCs was higher in BML regions compared with non-BML regions (median difference 5.6-fold; P < 0.001); the CFU-F assay showed a similar trend (median difference 4.3-fold; P = 0.013). Immunohistochemistry revealed CD271+ cell accumulation in bone adjacent to cartilage defects and areas of osteochondral angiogenesis. BML MSCs had lower proliferation and mineralization capacities in vitro and altered expression of TNFSF11/RANKL and CXCR4/stromal cell-derived factor 1 receptor. OA MSCs showed up-regulated transcripts for CXCR1 and CCR6 compared with MSCs derived from healthy or osteoporotic bone.
  
  
  
  This study is the first to show numeric and topographic alterations in native MSCs in the diseased bone of patients with hip OA. Given the associated functional perturbation of MSCs, these data suggest that subchondral bone MSC manipulation may be an OA treatment target.
authors: University of Ottawa, Ottawa, Ontario, Canada.
authors: T Mark
authors: TM
authors: Campbell
authors: University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors: Sarah M
authors: SM
authors: Churchman
authors: University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors: Alejandro
authors: A
authors: Gomez
authors: University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors: Dennis
authors: D
authors: McGonagle
authors: University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors: Philip G
authors: PG
authors: Conaghan
authors: University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors: Frederique
authors: F
authors: Ponchel
authors: University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors: Elena
authors: E
authors: Jones
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000150:complications / Q000235:genetics / Q000473:pathology*