The trachea is a very complex structure of the respiratory tract, composed of C-shaped cartilaginous rings, made of hyaline cartilage. In contrast to other intensely studied cartilages such as the ones found in the developing growth plate or in the adult joints, very little information is available on the innate propensity of this structure to mineralize.
Clinical studies have reported that tracheal calcification is considered a common finding in elderly patients. It is also observed in younger indivduals suffering from rare pathological conditions where the expression or activity of the Matrix Gla Protein (MGP) is impaired, suggesting an important role of this potent Vitamin K-dependent calcification inhibitor in the protection against aberrant mineralization of the trachea.
In that context, we ought to understand the cellular and molecular mechanisms at the origin of tracheal mineralization that has been unexplored so far and the potential role played by the BMP and calcification inhibitor MGP in this process.
In this study, we thus carried out a thorough anatomical and histological analysis in order to determine the spatiotemporal onset and progression of trachea mineralization during postnatal and adult development of wild-type mice of different strains and in Mgp-deficient mice. This extensive and straightforward analysis led to very unanticipated results.
Indeed, in contrast to what has been described in humans, our data undeniably demonstrate that, in the mouse, tracheal mineralization initiates in the cartilaginous rings of wild-type mice as early as one month after birth and progresses through a rostrocaudal direction throughout the trachea to eventually spread in the bronchi after only 2 months.
This process seems to be accompanied by the terminal differenciation of the tracheal chondrocytes, as we observed by qPCR and in situ hybridization a strong Collagen X expression preceeding the dynamic mineralization of the cartilage rings. Similar studies performed with Mgp+/+, Mgp+/- and Mgp-/- littermates revealed that a decrease in MGP production in the tracheal environment accelerates the mineralization process of the rings.
The present study is the first to describe mouse tracheal calcification and provide evidence that in the mouse, contrary to the typical notion, tracheal cartilage is not a permanent hyaline cartilage throughout life, as it is physiologically able to mineralize early in life possibly through a BMP-dependent mechanism.