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THU0052 Heparin affin regulatory peptide (harp) in acute and chronic articular diseases
  1. M Héroult1,
  2. F Lioté2,
  3. R Champy2,
  4. D Barritault1,
  5. J Courty1
  1. 1Laboratoire de Recherche Sur La Croissance Cellulaire, La Réparation Et La Régénération Tissulaires (CRRET), UPRES-a CNRS 7053, Université Paris XII-Val de Marne, Creteil, France
  2. 2Laboratoire de Radiologie Expérimentale Et de Physiopathologie Articulaire (JE2149) (Centre Viggo Petersen), Université Paris VII and Hôpital Lariboisière (Assistance Publique-Hôpitaux de Paris [AP-HP]), Paris, France

Abstract

Background Heparin affin regulatory peptide (HARP), also known as pleiotrophin (PTN) is a potent mitogen for various cell types and an angiogenic polypeptide implicated in tumour development.1–4

Objectives Since the progression of the pannus is associated with angiogenic processes and synovial membrane hypertrophy,5,6 the involvement of HARP in comparison with two other growth factors including MK and VEGF in rheumatoid pathologies was investigated.

Methods Presence of HARP in human synovial fluids and sera from patients was investigated by immunoassay. The distribution of HARP mRNA and protein was studied by in situ hybridization and immunohistochemistry respectively.

Results Comparative analysis showed that HARP as well as MK concentrations were significantly higher (p < 0.001) in synovial fluids from patients with inflammatory arthritis including rheumatoid arthritis (n = 14), ankylosing spondylitis (n = 8), chondrocalcinosis (n = 7) and gout (n = 11) than from patients with osteoarthritis (n = 29). In contrast, no significant difference was observed between inflammatory and non inflammatory diseases for VEGF. In addition, serum HARP and MK concentrations were significantly higher in patients with arthritis (n = 37) than in normal subjects (n = 18) (p < 0.001). Immunohistological studies demonstrated HARP within the synovial lining cells, endothelial cells of new capillaries, and macrophages of inflammatory synovial tissue. In situ hybridization studies revealed that synovial lining cells and vascular endothelial cells expressed high levels of HARP mRNA.

Conclusion These results suggest that HARP, in concert with other cytokines and growth factors, may play a role in the pathophysiology of acute and chronic synovitis in conditions such as crystal-induced arthritis and rheumatoid arthritis, respectively.

References

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  2. Courty J, Dauchel MC, Caruelle D, Pederiset M, Barritault D. Biochem Biophy Res Commun. 1991;180:145–51

  3. Bernard-Pierrot I, Delbé J, Caruelle D, Barritault D, Courty J. J Biol Chem. in press

  4. Choudhuri R, Zhang HT, Donnini S, Ziche M, Bicknell R. Cancer Res. 1997;57:1814–19

  5. Peacok DJ, Banquerigo ML, Brahn E. J Exp Med. 1992;175:1135–8

  6. Koch AE. Ann Rheu Dis. 2000;59(Suppl 1):I65–71

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