Amelioration of inflammation, angiogenesis and CTGF expression in an arthritis model by a TSP1-derived peptide treatment.
OBJECTIVE
To evaluate the effect of a thrombospondin 1 (TSP1)-derived peptide on inflammation and angiogenesis in an animal model of erosive arthritis and to assess the relationship between TSP1 and connective tissue growth factor (CTGF) in the pathophysiology of rheumatoid arthritis.


METHODS
Erosive arthritis in Lewis rats was induced by peptidoglycan-polysaccharide (PG-PS). Animals were divided into four groups: (1) negative control and groups receiving, (2) no treatment, (3) treatment with a TSP1-derived peptide, and (4) treatment with a scrambled peptide. Samples obtained from ankle joint, spleen and liver were studied using histology, histomorphometry, immunohistochemistry and RT-PCR.


RESULTS
Histological data indicated that the TSP1-derived peptide treatment decreased neovascularization, leukocyte infiltration and thickening of the synovial lining of the joint, and reduced granuloma formation in the spleen and liver when compared to control groups. Higher concentrations of CTGF and TSP1 proteins were observed in the affected areas of animals which did not receive TSP1-derived peptide treatment. Also, immunofluorescence and RT-PCR analyses showed an increase in CTGF protein expression and regulation, respectively, in the tissues of untreated animals when compared to the TSP1-derived peptide treated animals. By immunofluorescence, TSP1 expression was decreased in the TSP1-derived peptide treated animals. Moreover, macrophage/monocyte-specific staining revealed a decrease in cell infiltration in the articular tissue of the TSP1-derived peptide treated animals.


CONCLUSIONS
Both inflammation and angiogenesis were decreased after TSP1-derived peptide treatment indicating a potential pathway by which TSP1 interaction with neutrophils induces CTGF in RA affected tissues.
Rico
Mario C
MC
Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. marior@temple.edu
Castaneda
Julian L
JL
Manns
Joanne M
JM
Uknis
Audrey B
AB
Sainz
Irma M
IM
Safadi
Fayez F
FF
Popoff
Steve N
SN
Dela Cadena
Raul A
RA
D000818:Animals; D000843:Ankle Joint / Q000187:drug effects / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D055513:Connective Tissue Growth Factor; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006099:Granuloma / Q000188:drug therapy / Q000378:metabolism; D006529:Hepatomegaly / Q000188:drug therapy / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D010457:Peptidoglycan; D011134:Polysaccharides; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013163:Splenomegaly / Q000188:drug therapy / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010457:Peptidoglycan; D011134:Polysaccharides; D012333:RNA, Messenger; D019700:Thrombospondin 1; D055513:Connective Tissue Growth Factor