Abstract
IntroductionGelatinous 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.MethodsAt 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.ResultsIn 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).ConclusionsGelatinous 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.
Highlights
Gelatinous Heberden’s nodes (HNs), termed synovial cysts, are a common form of generalized osteoarthritis (OA)
Given that HNs are associated with new bone formation and that the constituents of the gelatinous material are similar to synovial fluid (SF) [2,14], we hypothesized whether HN cysts contain a population of multipotential stromal cell (MSC) similar to those found in other synovial joints
HN cells cultured in osteogenic medium exhibited strong alizarin red staining, similar to SF-derived MSCs but less than those derived from iliac crest BM (ICBM), indicating that cells were committed to an osteogenic lineage
Summary
Gelatinous Heberden’s nodes (HNs), 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. Nodal OA may present acutely with painful joint swelling or Skeletal repair, remodeling, and new bone formation are thought to be linked to multipotential stromal cell (MSC) function, whereby highly proliferative cells from a variety of sources (such as bone marrow (BM), synovium, and adipose tissue) can form mesenchymal lineage tissues [5]. Given that HNs are associated with new bone formation and that the constituents of the gelatinous material are similar to SF [2,14], we hypothesized whether HN cysts contain a population of MSCs similar to those found in other synovial joints
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