Experimental and Molecular Pathology
Costal cartilage is much understudied compared to the load bearing cartilages. Abnormally grown costal cartilages are associated with the inherited chest wall deformities pectus excavatum and pectus carinatum resulting in sunken or pigeon chest respectively. A lack of understanding of the ultrastructural and molecular biology properties of costal cartilage is a major confounder in predicting causes and outcomes of these disorders. Due to the avascular nature of cartilage, chondrocytes metabolize glycolytically, producing an acidic environment. During physical activity hydrogen ions move within cartilage driven by compressive forces, thus at any one time, chondrocytes experience transient changes in pH. A variety of ion channels on chondrocytes plasma membrane equip them to function in the rapidly changing conditions they experience. In this paper we describe reduced expression of the ASIC2 gene encoding the acid sensing ion channel isoform 2 (previously referred to as ACCN1 or ACCN) in patients with chest wall deformities. We hypothesized that chondrocytes from these patients cannot respond normally to changes in pH that are an integral part of the biology of this tissue. Activation of ASICs indirectly creates a cascade ultimately dependent on intracellular calcium transients. The objective of this paper was to compare internal calcium signaling in response to external pH changes in costal chondrocytes from patients with chest wall deformities and healthy individuals. Although the molecular mechanism through which chondrocytes are regulated by acidosis remains unknown, we observed reduced amplitudes of calcium rise in patient chondrocytes exposed to low pH that become further impaired upon repeat exposure.
Original Publication Citation
Asmar, A., Semenov, I., Kelly, R., & Stacey, M. (2019). Abnormal response of costal chondrocytes to acidosis in patients with chest wall deformity. Experimental and Molecular Pathology, 106, 27-33. https://doi.org/10.1016/j.yexmp.2018.11.011
Asmar, A.; Semenov, Iurii; Kelly, R. Jr.; and Stacey, Michael, "Abnormal Response of Costal Chondrocytes to Acidosis in Patients with Chest Wall Deformity" (2019). Bioelectrics Publications. 297.
0000-0002-0302-1355 (Semenov), 0000-0002-3807-6233 (Stacey)