title: Regulation of bone metabolism by the kallikrein-kinin system, the coagulation cascade, and the acute-phase reactants.
abstract: Inflammation-induced localized bone resorption in diseases such as marginal and apical periodontitis, rheumatoid arthritis, and osteomyelitis is due to activation and recruitment of osteoclasts by locally produced cytokines and inflammatory mediators. Thus several interleukins (1, 3, 4, 6, and 11), tumor necrosis factors (alpha, beta), colony-stimulating factors (M and GM), leukemia inhibitory factor, gamma-interferon, and transforming growth factor-beta have effects on bone resorption and bone formation in vivo and in vitro. The kallikrein-kinin system and the coagulation cascade are also activated in inflammation. We have found that peptides produced in the kallikrein-kinin system (bradykinin, kallidin) and thrombin, the end product in the coagulation cascade, can stimulate bone resorption in vitro. The stimulatory effect of bradykinin is linked both to B1 and B2 bradykinin receptors. Both kinins and thrombin stimulate prostaglandin biosynthesis in bone parallel with the bone resorptive effect. The stimulatory effect of bradykinin on bone resorption is completely lost when the prostaglandin response is abolished, whereas thrombin can stimulate bone resorption both via prostaglandin-dependent and independent mechanisms. In addition, bradykinin and thrombin act in concert with interleukin-1 to synergistically stimulate bone resorption and prostaglandin biosynthesis. We also have found that one of the acute-phase reactants, haptoglobin, can stimulate bone resorption in vitro, indicating the possibility of generalized bone loss in chronic inflammatory diseases. Moreover, haptoglobin synergistically potentiates bradykinin-induced and thrombin-induced prostanoid biosynthesis in osteoblasts. These observations indicate that the rate of bone resorption in inflammation-induced bone loss may not be due to a single factor but to the concerted action of several local or systemic factors.
authors.affiliation: Department of Oral Cell Biology, University of Umeå, Sweden.
authors.forename: U H
authors.initials: UH
authors.lastname: Lerner
mesh_terms: D000209:Acute-Phase Proteins / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001779:Blood Coagulation Factors / Q000502:physiology*; D001862:Bone Resorption / Q000378:metabolism*; D065168:Bradykinin Receptor Antagonists; D005174:Factor XII / Q000502:physiology; D006801:Humans; D016234:Kallikrein-Kinin System / Q000502:physiology*; D007705:Kinins / Q000502:physiology; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis
chemical_list: D000209:Acute-Phase Proteins; D001779:Blood Coagulation Factors; D065168:Bradykinin Receptor Antagonists; D007705:Kinins; D011453:Prostaglandins; D005174:Factor XII