Expression of the precursor of secretoneurin, secretogranin II, in the synovium of patients with rheumatoid arthritis and osteoarthritis.
OBJECTIVE
Secretoneurin (SN) is a neuropeptide that is chemotactic for mononuclear cells and it has been suggested to be involved in the mediation of pain; there is also evidence that SN is involved in the inflammation process. As secretogranin II (SGII) is the precursor of SN, we investigated expression of SGII mRNA and SN protein in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA).


METHODS
Snap frozen synovial tissue specimens from 12 patients with RA and 11 patients with OA were examined. RNA was isolated and cDNA copied by reverse transcription. The expression of SGII was determined by polymerase chain reaction and in situ hybridization (ISH). SGII expressing cells were compared with CD68 positive cells stained by immunohistochemistry. SN protein was also detected by immunohistochemistry.


RESULTS
A 524 bp SGII-specific fragment could be amplified by PCR from the cDNA of all specimens. ISH showed scattered expression of SGII in both RA and OA synovial tissue; its expression pattern was characterized by positive staining for SGII in both the lining and the sublining layer. Immunohistochemical double labeling with anti-CD68 antibodies revealed expression of SGII in CD68 negative, fibroblast-like cells, whereas CD68 positive macrophages did not. In RA and OA, the SGII staining by ISH was positive with a diffuse staining throughout the entire synovial tissue. SN protein expression was scattered in RA but more intense in OA synovium.


CONCLUSIONS
The expression of SGII mRNA in RA and OA synovial fibroblasts clearly supports the hypothesis that SN is involved in the synovial tissue inflammation in both diseases. The significant lower SN expression in RA could be due to an inhibitory mechanism with respect to the SN levels in synovial fluid. SN might be involved in the modulation of afferent nerve transmission and therefore might play a role in the sensation of pain, especially in patients with OA.
Sprott
H
H
Center for Experimental Rheumatology, Department of Rheumatology and Institute of Physical Medicine, University Hospital Zürich, Switzerland. ruzsph@ruz.unizh.ch
Pap
T
T
Rethage
J
J
Wintersberger
W
W
Gay
R E
RE
Bradley
L A
LA
Uebelhart
D
D
Gay
S
S
D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002864:Chromogranins; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053381:Secretogranin II; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002864:Chromogranins; D017931:DNA Primers; D018076:DNA, Complementary; D009479:Neuropeptides; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; D053381:Secretogranin II; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C081159:secretoneurin