Inhibition of BMP activity protects epithelial barrier function in lung injury.

Epithelial injury is a central finding in pulmonary disease and is accompanied by disruption of epithelial barrier function, leading to pulmonary oedema and inflammation. Injured epithelial cells lose their properties and gain mesenchymal characteristics, a phenotypic switch that contributes to lung remodelling after injury. Here we studied bone morphogenetic protein (BMP) signalling and, in particular, the role of BMP2 and the BMP modulator BMPER in injured lung epithelium. Increased BMP activity, reflected by up-regulation of the Smad1/5-Id1 axis, is detected after injury of lung epithelium in vitro and in vivo. Two members of the BMP family, BMP2 and BMPER, have opposing effects. BMP2 is up-regulated after epithelial injury and causes epithelial dysfunction and hyperpermeability, mediated by the Smad1/5-Id1-dependent down-regulation of E-cadherin. In contrast, BMPER expression is decreased following injury, which in turn impairs epithelial integrity, characterized by reduction of E-cadherin and epithelial leakage in vitro and in vivo. High levels of BMPER antagonized BMP2-Smad5-Id1 signalling and prevented BMP2-mediated decrease of E-cadherin and hyperpermeability, suggesting that BMPER restores epithelial homeostasis. Supporting this notion, pharmacological inhibition of BMP signalling by LDN193189 prevented reduction of E-cadherin and disruption of epithelial barrier function. Inhibition of excessive BMP activation could be a new approach to restore epithelial integrity and prevent disruption of epithelial barrier function after lung injury.

Characteristics and outcomes of chronic non-bacterial osteitis in children.

OBJECTIVE: To determine patient characteristics, clinical presentation, pattern of involvement, treatment, and outcome of patients with chronic non-bacterial osteitis (CNO). MATERIAL AND METHODS: Consecutive cases of CNO were analyzed at a single center for pediatrics and adolescent medicine from 2006 to 2013 in terms of patient characteristics, clinical presentation, pattern of involvement, treatment, and outcome. RESULTS: We identified 32 children aged 1.5-15 years who were diagnosed with CNO between 2006 and 2013. A maximum of 12 bones per patient were affected in a total of 114 documented locations. The pelvis and clavicle (affecting 34% of patients each) were the most frequently affected bones. The foot skeleton was the most commonly affected region in 60% of patients. Skin manifestations were found in 7 (21%) patient. Increased inflammatory signs at presentation were detected in 18 patients. Pathological findings were found in all 30 children examined using magnetic resonance imaging (MRI), in 10 of 11 children examined using radiography, and in 8 of 10 patients examined using skeletal scintigraphy. Bone biopsy was performed in 9 patients. For initial treatment, non-steroidal anti-inflammatory drugs (NSAIDs) or coxibs were used in 28 (87.5%) patients. Remission or satisfactory follow-up was achieved in all patients. CONCLUSION: Today, CNO is increasingly diagnosed using MRI and rarely through histological examinations. Therapeutic strategies include NSAIDs, which are often highly effective. All patients in the present study showed good clinical outcomes.