Bradykinin,a new potential mediator of inflammation-induced bone resorption

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, BPP_5a. Treatment with carboxypeptidase B did not affect the capacity of the peptide to stimulated ⁴⁵Ca release. DesArg⁹-bradykinin (1 m̈mole/liter) stimulated ⁴⁵Ca release to the same degree as did bradykinin. Bradykinin (3 m̈M) 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.