EGF and IL-1 alpha modulate the release of collagenase, gelatinase and TIMP-1 as well as the release of calcium by rabbit calvarial bone explants.
Matrix metalloproteinases (MMPs), among which is collagenase (MMP-1), are likely to be involved in various steps of the bone resorption process. As both production of these enzymes and bone resorption appear to be mediated by cytokines, we investigated the effects of two cytokines, IL-1 alpha and EGF, on the release of collagenase, gelatinase A (MMP-2), gelatinase B (MMP-9), TIMP-1 and calcium by rabbit calvariae. It was found that all these parameters increased under the influence of these cytokines. The release of calcium--used as a parameter of bone resorption--was highest in the combined presence of the cytokines. Although the absolute and relative enhancement by a combination of IL-1 alpha and EGF was most pronounced for collagenase (7-fold), both gelatinase A (5-fold) and gelatinase B (1.5-fold) had increased simultaneously. Calvariae produced a high level of MMP inhibitor (TIMP-1), especially under the influence of the cytokines; periosteum released little inhibitor. It is concluded that IL-1 alpha and EGF are likely to play a modulating role in the process of bone resorption.
van der Zee
E
E
Department of Periodontology, The Netherlands.
Jansen
I
I
Hoeben
K
K
Beertsen
W
W
Everts
V
V
D000704:Analysis of Variance; D000818:Animals; D001862:Bone Resorption / Q000201:enzymology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D017364:Collagenases / Q000187:drug effects / Q000378:metabolism*; D046508:Culture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D018093:Gelatinases / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000187:drug effects / Q000378:metabolism; D010521:Periosteum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism*; D011817:Rabbits; D019275:Radiopharmaceuticals; D012886:Skull / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium
D007375:Interleukin-1; D011480:Protease Inhibitors; D019275:Radiopharmaceuticals; D019715:Tissue Inhibitor of Metalloproteinase-1; D014316:Tritium; D004815:Epidermal Growth Factor; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D002118:Calcium; D013936:Thymidine