Collagenase synthesis of rheumatoid arthritis synoviocytes: dose-dependent stimulation by substance P and capsaicin.

  title={Collagenase synthesis of rheumatoid arthritis synoviocytes: dose-dependent stimulation by substance P and capsaicin.},
  author={Gerald Partsch and Marco Matucci-Cerinic and Simone Marabini and Susanne Jantsch and Alberto Moggi Pignone and Mario Cagnoni},
  journal={Scandinavian journal of rheumatology},
  volume={20 2},
The synthesis and release of collagenase in the presence of the neuropeptide substance P (SP) and capsaicin, were investigated in vitro using identical synoviocyte cultures from patients with rheumatoid arthritis (RA). On average 10(-12) M SP augmented statistically significantly the collagenase production by approximately a factor of five. An increase in the concentrations up to 10(-6) M SP resulted in a decreased collagenase synthesis, which, however, was still above the level of that of the… 

Substance P Induces the Secretion of Gelatinase A from Human Synovial Fibroblasts

It is assumed that distinct stimulation pathways are involved and that the neuropeptide (substance P), which is always present in the inflamed joint, plays its own and separate role in proliferative processes leading to the cartilage destruction.

Effect of substance P and somatostatin on migration of polymorphonuclear (PMN) cells in vitro

Although it is uncertain whether in vivo SP and SOM contribute directly to the invasion of PMN cells into the joint cavity, the influence of these neuropeptides on PMN migration in vitro is a further indication of the neuropeptic involvement in the genesis of inflammation.


Results suggest that substance P participates in extracellular matrix metabolism, and induced a decrease in collagen biosynthesis, concomitant to a down-regulation of pro-α1(I) collagen mRNA.

Tachykinin receptor modulators: novel therapeutics for rheumatoid arthritis.

  • Brunelleschi
  • Biology, Medicine
    Expert opinion on investigational drugs
  • 1999
Different observations suggest that one approach to the treatment of RA might be to inhibit the local effects of neurokinins in the affected joints, and this review will summarise the more relevant aspects of this topic.

Microscopic localization of active gelatinases in equine osteochondritis dissecans (OCD) cartilage.

Investigating the relationship between matrix metalloproteinase (MMP) activity and osteochondritis dissecans (OCD) in the equine joint revealed MMP activity, especially in the deep zone adjacent to the calcified subchondral bone.



Effects of capsaicin on the metabolism of rheumatoid arthritis synoviocytes in vitro.

The results indicate that the different effects of capsaicin on cellular proliferation and on metabolic activities are dependent on dose and suggest that the responses seen in rheumatoid arthritis synoviocytes in vitro might not be mediated by tachykinins if the synovial tissue is still able to produce neuropeptides in the absence of neuronal afferents.

Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells.

Production of PGE2 and collagenase in large amounts in vitro by cells dispersed with proteolytic enzymes from rheumatoid arthritic synovectomy specimens suggests that they may be involved in joint destruction in vivo.

Substance P activation of rheumatoid synoviocytes: neural pathway in pathogenesis of arthritis.

The specific stimulation of synoviocytes by the neuropeptide substance P represents a pathway by which the nervous system might be directly involved in the pathogenesis of rheumatoid arthritis.

Collagenase production by synovial fibroblasts treated with phorbol myristate acetate.

Synovial fibroblasts treated with phorbol myristate acetate may provide a good model for studies on the mechanism of induction of collagenase production and was associated with a cessation of cell proliferation, measured by protein content/culture and cell number.

Inhibition of carrageenan induced inflammation in the rat knee joint by substance P antagonist.

Results indicate a significant neurogenic component in this model of acute joint inflammation in animals whose knee had previously been injected with 1% capsaicin, while chronic joint denervation produced a 37% reduction.

Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts

The ability of cachectin/TNF to stimulate collagenase and PGE2 production suggests that it may play a role in tissue destruction and remodelling, as these processes occur in inflammatory diseases.

Mechanisms of depletion of substance P by capsaicin.

As the onset of thermal analgesia in guinea pigs precedes depletion of substance P, direct neural actions of capsaicin probably account for its effects on sensory function.