Genetic deletion of osteoprotegerin attenuates asthma development through suppression of inflammatory response in...

To clarify the detailed molecular mechanisms underlying the development of asthma, we assessed the potential immune effects of prenatal osteoprotegerin (OPG) inhibition in the pathogenesis of asthma. The effects of OPG deficiency on the development of asthma were evaluated using an ovalbumin-induced asthma model in OPG knockout mice. Histological analysis demonstrated that OPG was mainly detected in airway epithelial cells in wild type mice. After ovalbumin sensitization and challenge, accumulation of inflammatory cells, gene expression of T helper 2-related cytokines and mucus hypersecretion in lung tissues were inhibited by OPG deficiency. Importantly, the serum level of IgE was not increased in OPG KO mice after ovalbumin sensitization and challenge. Based on these findings, OPG knockout mice were protected against methacholine-induced airway hyperresponsiveness. OPG expression is thought to be essential for induction of the allergic immune response in asthma.