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Detection, identification and in vivo treatment responsiveness of bone morphogenetic protein (BMP)-activated cell populations in the synovium of patients with rheumatoid arthritis
  1. P C P M Verschueren1,
  2. R J U Lories1,
  3. M Daans1,
  4. I Théate3,
  5. P Durez2,
  6. R Westhovens1,
  7. F P Luyten1
  1. 1
    Laboratory for Skeletal Development and Joint Disorders, Division of Rheumatology Department of Musculoskeletal Sciences, Katholieke Universiteit Leuven, Belgium
  2. 2
    Department of Rheumatology
  3. 3
    Department of Pathology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Belgium
  1. F P Luyten, Department of Rheumatology, Department of Musculoskeletal Sciences University Hospitals KU Leuven, Herestraat 49, B-3000 Leuven, Belgium; frank.luyten{at}


Objective: To characterise the bone morphogenetic protein (BMP) target cells positive for phosphorylated (P)-SMAD1/5, in rheumatoid arthritis (RA) synovium.

Methods: Synovial biopsies were obtained by needle arthroscopy. Anti-P-SMAD1/5 antibodies were used for Western blot (WB) on protein extracts from RA and normal synovium and for immunostaining of synovial biopsy sections. Positive cells were further identified by double staining for CD3, CD20, CD68, CD138, CD90, α smooth muscle actin (SMA), endoglin (CD105) and von Willebrand factor (VWF). In sections from early patients with RA taken before and under antirheumatic treatment, the degree of inflammation and activation of the BMP pathway were quantified.

Results: P-SMAD1/5 protein was detected by WB in RA and to a lesser extent in normal synovium. Different P-SMAD1/5 positive cell populations were identified in RA synovium, mainly in perivascular and sublining cells. P-SMAD1/5 positive perivascular cells were αSMA positive and located around VWF positive endothelial cells. Some CD90 positive synovial fibroblasts were P-SMAD1/5 positive, as was part of the CD68 positive synovial cells but other cells of the haematopoietic lineage showed no SMAD1/5 phosphorylation. Treatment resulted in an absolute but not relative decrease in BMP activation in the synovium.

Conclusion: BMP-activated cells belong to distinct stromal compartments in RA synovium and some of them express markers associated with the mesenchymal progenitor cell lineage. Antirheumatic treatment effectively downregulates synovial inflammation, but BMP activation in the synovium does persist albeit reduced.

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  • Competing interests: None.

  • Funding: PCPMV is supported by a PhD grant from the Research Foundation – Flanders (FWO-Vlaanderen) and RJUL is a postdoctoral fellow of the FWO-Vlaanderen. This work was supported by grants from the FWO-Vlaanderen and a GOA grant from the KU Leuven.

  • ▸ Additional data (reagents and detailed methods) are published online only at

  • Ethics approval: Ethics approval was obtained.