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 Ca-45 from neonatal mouse calvariae. The possibility that the factor(s) was interleukin-1 alpha (IL-1 alpha, IL-1 beta or prostaglandin E-2 (PGE(2)) was next investigated. The human fibroblast conditioned media (HFCM) stimulated PGE(2) biosynthesis in bone. The stimulatory effect by HFCM on Ca-45 release, however, was not affected by blocking prostaglandin biosynthesis with indomethacin. In contrast, Ca-45 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 PGE(2) in HFCM was too low to be solely responsible for the Ca-45 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 Ca-45 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.