Rheumatology International

, Volume 14, Issue 5, pp 191–199

Influence of interleukin-1β, tumour necrosis factor alpha and prostaglandin E2 on chondrogenesis and cartilage matrix breakdown in vitro

  • H. Mohamed-Ali
Original Article

DOI: 10.1007/BF00262297

Cite this article as:
Mohamed-Ali, H. Rheumatol Int (1995) 14: 191. doi:10.1007/BF00262297


Inflammatory mediators such as the cytokines interleukin-1 (IL-1) or (TNFα), and prostaglandins [predominantly prostaglandin E2 (PGE2)] are generally considered to be involved in the breakdown of cartilage matrix in chondrodestructive diseases, especially rheumatoid arthritis and osteoarthritis. Their mode of action is not yet completely understood. Blastemal cells or differentiated chondroblasts/chondrocytes of limb buds from mouse embryos (day 12) in organoid cultures provide an efficient system to investigate the mechanism of action of these substances. Using recombinant human IL-1β, TNFα and PGE2 alone or together (in pairs) in this culture system, we found that none of these substances alone could affect chondrogenesis. TNFα, however, when combined with IL-1β, proved to be the more potent cytokine causing a transformation of embryonal chondrogenic cells into fibroblast-like cells and thus inhibiting the expression of the cartilage cell phenotype. This might be due to inhibition of both the morphgenetic and cytodifferentiation phases of chondrogenesis. The well-known synergistic interaction between both cytokines seems to be phase limited and may not occur in the postchondrogenesis phase. In addition, our results showed that TNFα alone or combined with PGE2 caused a marked breakdown of the cartilage matrix. These in vitro findings might be useful to elucidate the complexity of interactions between different cytokines and PGE2 involved in cartilage destruction processes in vivo.

Key words

CytokinesChondrogenesisMatrix degradationOrganoid culture

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • H. Mohamed-Ali
    • 1
  1. 1.Institute of AnatomyFree University of BerlinBerlinGermany