title: Intrinsic multipotential mesenchymal stromal cell activity in gelatinous Heberden's nodes in osteoarthritis at clinical presentation.
abstract: BACKGROUND
  Gelatinous Heberden's nodes (HNs), also termed synovial cysts, are a common form of generalized osteoarthritis (OA). We sought to determine whether HN cases at clinical presentation contained multipotential stromal cells (MSCs) and to explore whether such cells were more closely related to bone marrow (BM) or synovial fluid (SF) MSCs by transcriptional analysis.
  
  
  METHODS
  At clinical presentation, gelatinous material was extracted/extruded from the distal phalangeal joint of OA patients with HNs. From this, plastic adherent cells were culture-expanded for phenotypic and functional characterization and comparison with BM- and SF-MSCs. Mesenchymal related gene expression was studied by using a custom-designed TaqMan Low Density Array to determine transcriptional similarities between different MSC groups and skin fibroblasts.
  
  
  RESULTS
  In all cases, HN material produced MSC-like colonies. Adherent cultures displayed an MSC phenotype (CD29(+), CD44(+), CD73(+), CD81(+), and CD90(+) and CD14(-) CD19(-), CD31(-), CD34(-), CD45(-), and HLADR(-)) and exhibited osteogenic, chondrogenic lineage differentiation but weak adipogenesis. Gene cluster analysis showed that HN-MSCs were more closely related to SF- than normal or OA BM-MSCs with significantly higher expression of synovium-related gene markers such as bone morphogenic protein 4 (BMP4), bone morphogenetic protein receptor type 1A (BMPR1A), protein/leucine-rich end leucine-rich repeat protein (PRELP), secreted frizzled-related protein 4 (SFRP4), and tumor necrosis factor alpha-induced protein 6 (TNFAIP6) (P <0.05).
  
  
  CONCLUSIONS
  Gelatinous HNs derived from hand OA at clinical presentation contain a population of MSCs that share transcriptional similarities with SF-derived MSCs. Their aberrant entrapment within the synovial cysts may impact on their normal role in joint homeostasis.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Baboolal
authors.forename: Sally A
authors.initials: SA
authors.lastname: Boxall
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Churchman
authors.forename: Conor T
authors.initials: CT
authors.lastname: Buckley
authors.forename: Elena
authors.initials: E
authors.lastname: Jones
authors.forename: Dennis
authors.initials: D
authors.lastname: McGonagle
mesh_terms: D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D016000:Cluster Analysis; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013581:Synovial Cyst / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism