Detection of high levels of heparin binding growth factor-1 (acidic fibroblast growth factor) in inflammatory arthritic joints.
The synovium from patients with rheumatoid arthritis (RA) and LEW/N rats with streptococcal cell wall (SCW) arthritis, an experimental model resembling RA, is characterized by massive proliferation of synovial connective tissues and invasive destruction of periarticular bone and cartilage. Since heparin binding growth factor (HBGF)-1, the precursor of acidic fibroblast growth factor (FGF), is a potent angiogenic polypeptide and mitogen for mesenchymal cells, we sought evidence that it was involved in the synovial pathology of RA and SCW arthritis. HBGF-1 mRNA was detected in RA synovium using the polymerase chain reaction technique, and its product was immunolocalized intracellularly in both RA and osteoarthritis (OA) synovium. HBGF-1 staining was more extensive and intense in synovium of RA patients than OA and correlated with the extent and intensity of synovial mononuclear cell infiltration. HBGF-1 staining also correlated with c-Fos protein staining. In SCW arthritis, HBGF-1 immunostaining was noted in bone marrow, bone, cartilage, synovium, ligamentous and tendinous structures, as well as various dermal structures and developed early in both T-cell competent and incompetent rats. Persistent high level immunostaining of HBGF-1 was only noted in T-cell competent rats like the disease process in general. These observations implicate HBGF-1 in a multitude of biological functions in inflammatory joint diseases.
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892.
H
H
Sano
R
R
Forough
J A
JA
Maier
J P
JP
Case
A
A
Jackson
K
K
Engleka
T
T
Maciag
R L
RL
Wilder
D000818:Animals; D001170:Arthritis, Infectious / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D015153:Blotting, Western; D005260:Female; D016220:Fibroblast Growth Factor 1; D005346:Fibroblast Growth Factors / Q000032:analysis* / Q000235:genetics; D006133:Growth Substances / Q000032:analysis* / Q000235:genetics; D006493:Heparin / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation; D008934:Mitogens / Q000032:analysis*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D016760:Proto-Oncogene Proteins c-fos; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000032:analysis; D013290:Streptococcal Infections / Q000473:pathology*; D013583:Synovial Membrane / Q000473:pathology*; D014158:Transcription, Genetic
D006133:Growth Substances; D008934:Mitogens; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1; D005346:Fibroblast Growth Factors; D006493:Heparin; D011505:Protein-Tyrosine Kinases