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

Autor: Lin Y; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905.; Department of Orthopedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P. R. China., Lewallen EA; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Camilleri ET; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Bonin CA; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Jones DL; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Dudakovic A; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Galeano-Garces C; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Wang W; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905.; Department of Orthopedics, WuHan Orthopedics Hospital/Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, China., Karperien MJ; Department of Developmental BioEngineering, University of Twente, Enschede, The Netherlands., Larson AN; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Dahm DL; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Stuart MJ; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Levy BA; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Smith J; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Ryssman DB; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Westendorf JJ; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Im HJ; Department of Biochemistry, Rush University Medical Center, Chicago, Illinois, 60612., van Wijnen AJ; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Riester SM; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905., Krych AJ; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905.
Jazyk: angličtina
Zdroj: Journal of orthopaedic research : official publication of the Orthopaedic Research Society [J Orthop Res] 2016 Nov; Vol. 34 (11), pp. 1950-1959. Date of Electronic Publication: 2016 Mar 03.
DOI: 10.1002/jor.23209
Abstrakt: 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. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1950-1959, 2016.
Competing Interests: Dr. Bruce Levy receives royalties from Arthrex and VOT Solutions. Dr. Aaron Krych is a paid consultant for Arthrex and Vericel. Dr. Michael Stuart is a paid consultant for Arthrex and receives royalties from Arthrex. The remaining authors have no conflicts relevant to this publication.
(© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)
Databáze: MEDLINE
Externí odkaz: