title: Bradykinin, a new potential mediator of inflammation-induced bone resorption. Studies of the effects on mouse calvarial bones and articular cartilage in vitro.
abstract: The effect of bradykinin and desArg9-bradykinin on bone was studied in cultures of calvarial bones taken from 6-7-day-old mice. Bradykinin, at and above a 3-nM concentration, caused a dose-dependent stimulation of bone mineral mobilization and matrix degradation. Bradykinin-stimulated resorption was inhibited by calcitonin, an increased concentration of phosphate in the culture medium, hydrocortisone, dexamethasone, indomethacin, meclofenamic acid, naproxen, and 5, 8, 11, 14-eicosatetraenoic acid. The results suggest that bradykinin stimulates osteoclast-mediated bone resorption by a process that is dependent on endogenous prostaglandin production. The stimulatory effect of bradykinin, but not of parathyroid hormone and prostaglandin E2, was potentiated by the angiotensin-converting enzyme inhibitor, BPP5a. Treatment with carboxypeptidase B did not affect the capacity of the peptide to stimulate 45Ca release. DesArg9-bradykinin (1 mumole/liter) stimulated 45Ca release to the same degree as did bradykinin. Bradykinin (3 microM) did not affect the degradation of cartilage proteoglycans, as assessed by the release of 35S-sulfate from prelabeled calf articular cartilage in organ culture. These findings suggest that generation of bradykinin in inflammatory lesions of rheumatoid arthritis and periodontitis may contribute to the bone resorptive process seen in the joints and alveolar bone; however, bradykinin does not directly activate chondrocytes into a catabolic state.
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D011509:Proteoglycans; C024626:bradykinin, des-Arg(9)-; D001920:Bradykinin