The bone resorbing activity released by gingival fibroblasts isolated from patients with periodontitis is independent of interleukin-1.
Supernatants from gingival fibroblast cultures obtained from 14 patients with periodontal disease contained factor(s) capable of stimulating bone resorption in vitro, as assessed by the release of 45Ca from neonatal mouse calvariae. The possibility that the factor(s) was interleukin-1 alpha (IL-1 alpha), IL-1 beta or prostaglandin E2 (PGE2) was next investigated. The human fibroblast conditioned media (HFCM) stimulated PGE2 biosynthesis in bone. The stimulatory effect by HFCM on 45Ca release, however, was not affected by blocking prostaglandin biosynthesis with indomethacin. In contrast, 45Ca release induced by IL-1 alpha, IL-1 beta, thrombin and bradykinin was significantly reduced by indomethacin, whereas the effects of PTH and PTHrP were unaffected by indomethacin. The concentration of PGE2 in HFCM was too low to be solely responsible for the 45Ca release response. In addition, the amount of bone resorbing activity produced by the gingival fibroblasts was unaffected by cyclo-oxygenase inhibitors. Similar to IL-1 alpha and IL-1 beta, the stimulatory effect of HFCM was inhibited by gamma-interferon. HFCM did not stimulate cyclic AMP formation in the mouse calvarial bones. Antisera which specifically blocked human IL-1 alpha or IL-1 beta induced 45Ca release, and the specific IL-1 receptor antagonistic protein, did not inhibit the stimulatory effect of HFCM. These data show that gingival fibroblasts secrete bone resorbing factor(s) which is not due to IL-1 and which stimulates bone resorption by a prostaglandin- and cyclic AMP-independent mechanism.
Sjöström
S
S
Department of Oral Cell Biology, Umeå University, Sweden.
Hänström
L
L
Lerner
U H
UH
D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption / Q000139:chemically induced / Q000503:physiopathology*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D010518:Periodontitis / Q000150:complications / Q000503:physiopathology*; D011453:Prostaglandins / Q000032:analysis / Q000096:biosynthesis; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D002132:Calcium Radioisotopes; D017077:Culture Media, Conditioned; D007106:Immune Sera; D007375:Interleukin-1; D011453:Prostaglandins; D000242:Cyclic AMP