Journal article
RNA-seq Analysis of Clinical-Grade Osteochondral Allografts Reveals Activation of Early Response Genes
Journal of orthopaedic research, Vol.34(11), pp.1950-1959
11/2016
DOI: 10.1002/jor.23209
PMCID: PMC4993686
PMID: 26909883
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). The elevated expression of " early response genes" and reduced levels of ECM-related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. (C) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Details
- Title: Subtitle
- RNA-seq Analysis of Clinical-Grade Osteochondral Allografts Reveals Activation of Early Response Genes
- Creators
- Yang Lin - Mayo Clin, Dept Orthoped Surg, 200 First St SW, Rochester, MN 55905 USAEric A. Lewallen - Mayo ClinicEmily T. Camilleri - Mayo ClinicCarolina A. Bonin - Mayo ClinicDakota L. Jones - Mayo ClinicAmel Dudakovic - Mayo ClinicCatalina Galeano-Garces - Mayo ClinicWei Wang - Mayo ClinicMarcel J. Karperien - University of TwenteAnnalise N. Larson - Mayo ClinicDiane L. Dahm - Mayo ClinicMichael J. Stuart - Mayo ClinicBruce A. Levy - Mayo ClinicJay Smith - Mayo ClinicDaniel B. Ryssman - Mayo ClinicJennifer J. Westendorf - Mayo ClinicHee-Jeong Im - Rush UniversityAndre J. van Wijnen - Mayo ClinicScott M. Riester - Mayo ClinicAaron J. Krych - Mayo Clinic
- Resource Type
- Journal article
- Publication Details
- Journal of orthopaedic research, Vol.34(11), pp.1950-1959
- DOI
- 10.1002/jor.23209
- PMID
- 26909883
- PMCID
- PMC4993686
- NLM abbreviation
- J Orthop Res
- ISSN
- 0736-0266
- eISSN
- 1554-527X
- Publisher
- Wiley
- Number of pages
- 10
- Grant note
- LLP-25 / ReumaFonds Mayo Graduate School, Clinical and Translational Sciences Track R01AR049069 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) R01 AR049069; R03 AR066342-02; T32 AR56950; F32 AR066508 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA T32HL105355 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Center for Regenerative Medicine at Mayo Clinic
- Language
- English
- Date published
- 11/2016
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984949239202771
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