RNA-seq analysis of clinical-grade osteochondral allografts reveals activation of early response genes

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Yang LinAaron J Krych

Abstract

Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA-seq) and real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) to assess genome-wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of "early response genes" that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND)....Continue Reading

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Citations

Mar 14, 2017·Nature Reviews. Genetics·Joshua Y C Yang, Minnie M Sarwal
Jul 4, 2017·Journal of Cellular Biochemistry·Mark E MorreyMatthew P Abdel
Dec 12, 2017·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Scott M RiesterAhmad Nassr
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Jul 4, 2017·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Jakob T SiekerBraden C Fleming
Jan 26, 2021·JAMA Network Open·Dmitry RychkovMinnie M Sarwal

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