Defining the baseline transcriptional fingerprint of rabbit hamstring autograft

Abstract

Anterior cruciate ligament (ACL) injuries are common and of high relevance given their significant effects on patient function, quality of life, and posttraumatic arthritis. To date, investigators have reported on the expression of genes classically associated with tendon and ligament reconstruction, including decorin (DCN) and collagen type 1 (COL1A1 and COL1A2). However, the transcriptional fingerprint for hamstring tendons, one of the most common autografts used for ACLR, remains to be determined. The purpose of this study was to characterize the baseline transcriptional state of semitendinosus autografts in a rabbit model for ACLR and to employ such characterization to guide scientifically-driven target gene selection for future analyses.Next generation RNA sequencing was performed on whole semitendinosus autografts from four New Zealand White rabbits (mean age: 193 ± 0 days, mean weight: 2.78 kg ± 0.15 kg) and subsequently analyzed using gene enrichment and protein-protein interaction network analysis. Decorin, Secreted Protein Acidic and Cysteine Rich (SPARC), Collagen type 1, and Proline and Arginine Rich End Leucine Rich Repeat Protein (PRELP) and were determined to be the highest expressed genes with tendon-associated ontology. These results strengthen the association between genes such as DCN, COL1A1, and COL1A2 and tendon tissues as well as provide the novel addition of further high-expression, tendon characteristic genes such as SPARC and PRELP to provide guidance as to which molecules serve as high-signal candidates for future ACL research. In addition, this paper provides open-access to the expression fingerprint of hamstring autograft for ACLR in New Zealand White rabbits, thus providing a readily-accessible collaborative reference, in alignment with ethical animal research principles.