Nasal septum deviation as the consequence of BMP-controlled changes to cartilage properties

Nasal septum deviation (NSD) is a common abnormality of the septal cartilage often associated with disordered breathing. The etiology of NSD is unknown. BMP7 neural crest-knockout mice, a well-characterized model for midfacial hypoplasia and nasal airway obstruction, develops a deviated septum by 4 weeks of age. Using comparative gene expression, quantitative proteomics, and immunofluorescence analysis we investigated the septum prior, immediately preceding, and with established deviation. We provide a detailed description of cellular and molecular changes leading to septum deviation, including changes to extracellular matrix organization, cell metabolism, and chondrocyte differentiation. Loss of BMP7 was associated with acquisition of elastic cartilage properties, a switch to glucose metabolism, and molecular characteristics commonly associated with osteoarthritis (OA). Many alterations preceded the deviation establishing that molecular changes to chondrocyte properties predispose to the deviation. Interestingly, NSD was associated with a persistent increase in BMP2. Genetic reduction of BMP2 in BMP7ncko mice restores WNT signalling, energy metabolism, and rescues NSD, showing the importance of balanced BMP signaling for normal cartilage. Many of the cellular and molecular changes have been described for knee osteoarthritis, suggesting that these two pathologies might have a similar underlying etiology.