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Virchows Archiv B

, 64:45 | Cite as

Inhibition of the effects of rheumatoid synovial fluid cells on chondrogenesis and cartilage breakdown in vitro: possible therapeutical conclusions

A morphological—biochemical study
  • Hassan Mohamed-Ali
  • Peter Scholz
  • Hans-Joachim Merker
Article

Summary

Short-term co-cultivation of blastemal cells from 12-day-old mouse limb buds and human rheumatoid synovial fluid cells in high density cultures (Trowell culture system) resulted, depending on when co-cultivation started, either in (1) an inhibition of chondrogenesis (co-cultivation right from the start) or in (2) an extensive breakdown of cartilaginous matrix (co-cultivation after formation of embryonic cartilage). These synovial effects were markedly impeded if Avarol (a dioxygenase inhibitor) was applied singly or in combination with PAI-2 (a u-PA-inhibitor). PAI-2 alone, however, had no effect on the synovial-induced inhibition of chondrogenesis, but produced a pronounced inhibitory effect on matrix breakdown. The effects of both inhibitors were studied electron microscopically and biochemically (determination of sulfated-glycosaminoglycans in the high density cultures by Alcian Blue binding assay). The results of this study are consistent with the presumption that rheumatoid synovial cells are capable of inhibiting chondrogenesis and enhancing the breakdown of the cartilaginous matrix. Amongst others, the possible mediators involved are prostaglandins and plasminogen activators. The response to the inhibitors Avarol and PAI-2 is compatible with their mode of action. The chondroprotective action of these substances may be useful in developing potential antirheumatic drugs.

Key words

Synovial fluid cells Cartilage synthesis Cartilage breakdown Enzyme activator inhibition 

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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Hassan Mohamed-Ali
    • 1
  • Peter Scholz
    • 2
  • Hans-Joachim Merker
    • 1
  1. 1.Institute of AnatomyFree University of BerlinBerlin 33Germany
  2. 2.Department of Protein ChemistrySchering AG BerlinBerlinGermany

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