Decrease in expression of bone morphogenetic proteins 4 and 5 in synovial tissue of patients with osteoarthritis and rheumatoid arthritis.
Bone morphogenetic proteins (BMPs) have been identified as important morphogens with pleiotropic functions in regulating the development, homeostasis and repair of various tissues. The aim of this study was to characterize the expression of BMPs in synovial tissues under normal and arthritic conditions. Synovial tissue from normal donors (ND) and from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were analyzed for BMP expression by using microarray hybridization. Differential expression of BMP-4 and BMP-5 was validated by semiquantitative RT-PCR, in situ hybridization and immunohistochemistry. Activity of arthritis was determined by routine parameters for systemic inflammation, by histological scoring of synovitis and by semiquantitative RT-PCR of IL-1beta, TNF-alpha, stromelysin and collagenase I in synovial tissue. Expression of BMP-4 and BMP-5 mRNA was found to be significantly decreased in synovial tissue of patients with RA in comparison with ND by microarray analysis (p < 0.0083 and p < 0.0091). Validation by PCR confirmed these data in RA (p < 0.002) and also revealed a significant decrease in BMP-4 and BMP-5 expression in OA compared with ND (p < 0.015). Furthermore, histomorphological distribution of both morphogens as determined by in situ hybridization and immunohistochemistry showed a dominance in the lining layer of normal tissues, whereas chronically inflamed tissue from patients with RA revealed BMP expression mainly scattered across deeper layers. In OA, these changes were less pronounced with variable distribution of BMPs in the lining and sublining layer. BMP-4 and BMP-5 are expressed in normal synovial tissue and were found decreased in OA and RA. This may suggest a role of distinct BMPs in joint homeostasis that is disturbed in inflammatory and degenerative joint diseases. In comparison with previous reports, these data underline the complex impact of these factors on homeostasis and remodeling in joint physiology and pathology.
Department of Medicine, Nephrology and Rheumatology, Georg-August-University Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany. c.bramlage@med.uni-goettingen.de
Carsten P
CP
Bramlage
Thomas
T
Häupl
Christian
C
Kaps
Ute
U
Ungethüm
Veit
V
Krenn
Axel
A
Pruss
Gerhard A
GA
Müller
Frank
F
Strutz
Gerd-R
GR
Burmester
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000503:physiopathology*; D055415:Bone Morphogenetic Protein 4; D055417:Bone Morphogenetic Protein 5; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics / Q000503:physiopathology*; D012313:RNA / Q000235:genetics; D012016:Reference Values; D013583:Synovial Membrane / Q000502:physiology / Q000503:physiopathology*; D014158:Transcription, Genetic
C525809:BMP4 protein, human; C525814:BMP5 protein, human; D055415:Bone Morphogenetic Protein 4; D055417:Bone Morphogenetic Protein 5; D019485:Bone Morphogenetic Proteins; D012313:RNA