title: Patterns of Gene Expression from Human Costal Cartilage in Relation to the Chest Wall Deformity Pectus Carinatum
Creators: name: Grubbs, Janna E.
Publisher: name: Old Dominion University
publisherIdentifier: https://ror.org/04zjtrb98
publisherIdentifierScheme: ROR
Year: 2013

description: Cartilage deformities within the human chest wall, specifically pectus excavatum (PE) and pectus carinatum (PC) are common (1/400-1/1000) and yet, despite their clinical significance, are some of the least studied disorders pertaining to cartilage [1]. The costal cartilage connecting "false ribs" 8-10 to the sternum is often abnormally grown and can lead to formation of a severely sunken "funnel" chest (PE) or push outwards to form a "pigeon" chest (PC). Both conditions can have impact on the diaphragm, heart, lungs, and psychological function. An established ratio of PE and PC in males to females is 4:1, indicating a sex-linked male prevalence to these disorders.

In this study, costal cartilage samples from patients with PC were examined in comparison to samples from control cartilage, i.e., from those who did not have other known chondral dysplasias. We hypothesized that significant differences in expression of key cartilaginous related genes between the PC patients and an age-matched control would be observed. The genes of interest included COL1α1, COL2α1, SOX9, ACAN, compared to a housekeeping gene, Actin (ACTβ). We also analyzed expression of the small leucine-rich repeat proteoglycans (SLRPs) BGN and DCN. which bind to collagen fibers located in the extracellular matrix. The potent transcription factor of chondrogenesis studied was TGFβ1, as well as several other genes [2].

Our data revealed high levels of gene expression for DCN and COL2α1 in all samples of PC costal cartilage compared to an age-matched control. The male prevalence of these disorders was investigated in relation to the following X-linked cartilaginous related genes: NYX TIMP-1, BGN, and CACNA1F. The BGN SLRP did not exhibit significant differences in either patients or controls. The TIMP-1 gene was expressed with significant differences between patients and the age-matched control. The gene expression ratios of COL2α1/COL1α1, ACAN/COL2α1 and COL2α1/ACAN were also lower than published values reported for articular chondrocytes, fibrocartilage of intervertebral discs and rat chondrosarcomas. However, in our study, many ratios were established for the first time in this type of PC tissue. There were observed changes in patterns of gene expression of costal cartilage from the control samples age, 23 weeks to 81 years old, indicating the importance of age-matched controls.

For future studies, our data can be compared to similar experiments on the "true ribs" and how the costal cartilage of these ribs may change in terms of gene expression with age, and which gene expression changes are important for adolescents with PC and or PE. Also, an investigation of X-linked gene expression in female cartilage is needed to better understand the etiology of PC or PE in relation to X-inactivation. Better understanding of the biology of these disorders will help in identifying causes and sequelae, leading to modified therapeutic options, particularly for those patients who do not respond well to chest wall surgical repair. This study provides new baseline patterns of gene expression in the context of the biology of costal cartilage and is a major contribution in the cartilage biology field.