Regional Differential Genetic Response of Human Articular Cartilage to Impact Injury

Abstract

ObjectiveNormal physiological movement creates different weightbearing zones within a human knee: the medial condyle bearing the highest and the trochlea bearing the lowest weight. Adaptation to different physiological loading conditions results in different tissue and cellular properties within a knee. The objective of this study was to use microarray analysis to examine gene expression differences among three anatomical regions of human knee articular cartilage at baseline and following induction of an acute impact injury.DesignCartilage explants were harvested from 7 cadaveric knees (12 plugs per knee). A drop tower was utilized to introduce injury. Plugs were examined 24 hours after impact for gene expression using microarray. The primary analysis is the comparison of baseline versus impacted samples within each region separately. In addition, pairwise comparisons among the three regions were performed at baseline and after impact. False discovery rate (FDR) was used to evaluate significance of differential gene expression.ResultsIn the comparison of before and after injury, the trochlear had 130 differentially expressed genes (FDR ≤ 0.05) while the condyles had none. In the comparison among regions, smaller sets of differentially expressed genes (n ≤ 21) were found, with trochlea being more different than the condyles. Most of more frequently expressed genes in trochlea are developmental genes.ConclusionsWithin the experimental setup of this study, only the trochlea was displaying an acute genetic response on injury. Our data demonstrated the regional-specific response to injury in human articular cartilage.

Gene expression in the twilight of death

“…Several medical studies have reported increases in developmental control transcripts in response to stress such as injury of human knee articular cartilage [37], atherosclerotic-associated diseases [38], and lung cancer [39]. It is therefore, reasonable to suggest that increased abundance of developmental control and cancer-associated transcripts might reflect a universal response to stress that has not been previously recognized.…”

Using Genomic Techniques in Sports and Exercise Science: Current Status and Future Opportunities

“…For example, molecular studies have been performed across a number of tissues to identify potential genetic signatures associated with musculoskeletal trauma. This includes investigation of a few select genes from meniscus tissue in both degenerative and acute traumatic injuries (77), different regions of articular cartilage following impact injury (78), and microarray analysis of ACL tissue at various postinjury time points (79). These approaches have been enhanced using high throughput RNA sequencing.…”