RESEARCH - Detection, identification and in vivo treatment responsiveness of BMP-activated cell populations in the synovium of patients with RA

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ls of the Rheumatic Diseases 2009;68:117-123

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BASIC AND TRANSLATIONAL RESEARCH

Detection, identification and in vivo treatment responsiveness of bone

morphogenetic protein (BMP)-activated cell populations in the synovium

of patients with rheumatoid arthritis

P C P M Verschueren 1, R J U Lories 1, M Daans 1, I Théate 3, P Durez

2, R Westhovens 1, F P Luyten 1

1 Laboratory for Skeletal Development and Joint Disorders, Division of

Rheumatology Department of Musculoskeletal Sciences, Katholieke

Universiteit Leuven, Belgium

2 Department of Rheumatology

3 Department of Pathology, Cliniques Universitaires Saint-Luc,

Université Catholique de Louvain, Belgium

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, 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 SMA

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.

http://ard.bmj.com/cgi/content/abstract/68/1/117?etoc

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