title: The synovial microenvironment of osteoarthritic joints alters RNA-seq expression profiles of human primary articular chondrocytes.
abstract: Osteoarthritis (OA) is a disabling degenerative joint disease that prompts pain and has limited treatment options. To permit early diagnosis and treatment of OA, a high resolution mechanistic understanding of human chondrocytes in normal and diseased states is necessary. In this study, we assessed the biological effects of OA-related changes in the synovial microenvironment on chondrocytes embedded within anatomically intact cartilage from joints with different pathological grades by next generation RNA-sequencing (RNA-seq). We determined the transcriptome of primary articular chondrocytes derived from anatomically unaffected knees and ankles, as well as from joints affected by OA. The GALAXY bioinformatics platform was used to facilitate biological interpretations. Comparisons of patient samples by k-means, hierarchical clustering and principal component analyses together reveal that primary chondrocytes exhibit OA grade-related differences in gene expression, including genes involved in cell-adhesion, ECM production and immune response. We conclude that diseased synovial microenvironments in joints with different histopathological OA grades directly alter gene expression in chondrocytes. One ramification of this finding is that anatomically intact cartilage from OA joints is not an ideal source of healthy chondrocytes, nor should these specimens be used to generate a normal baseline for the molecular characterization of diseased joints.
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, United States. Electronic address: lewallen.eric@mayo.edu.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Lewallen
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, United States. Electronic address: bonin.carolina@mayo.edu.
authors.forename: Carolina A
authors.initials: CA
authors.lastname: Bonin
authors.affiliation: Jesse Brown VA Medical Center, Chicago, IL, United States. Electronic address: xin_li@rush.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, United States. Electronic address: smith.jay@mayo.edu.
authors.forename: Jay
authors.initials: J
authors.lastname: Smith
authors.affiliation: Department of Developmental Bioengineering, University of Twente, Enschede, The Netherlands. Electronic address: h.b.j.karperien@utwente.nl.
authors.forename: Marcel
authors.initials: M
authors.lastname: Karperien
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, United States. Electronic address: larson.noelle@mayo.edu.
authors.forename: A Noelle
authors.initials: AN
authors.lastname: Larson
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, United States. Electronic address: lewallen.david@mayo.edu.
authors.forename: David G
authors.initials: DG
authors.lastname: Lewallen
authors.affiliation: Department of Orthopedic Surgery, National University of Singapore, Singapore. Electronic address: simon.cool@imb.a-star.edu.sg.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Cool
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, United States; Department of Biochemistry & Molecular Biology, Mayo Clinic, Rochester, MN, United States. Electronic address: westendorf.jennifer@mayo.edu.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Westendorf
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, United States. Electronic address: krych.aaron@mayo.edu.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Krych
authors.affiliation: Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States. Electronic address: leontovich.alexey@mayo.edu.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Leontovich
authors.affiliation: Jesse Brown VA Medical Center, Chicago, IL, United States; Department of Biochemistry, Rush University, Chicago, IL, United States; Department of Orthopedic Surgery, Rush University, Chicago, IL, United States; Department of Internal Medicine, Rush University, Chicago, IL, United States. Electronic address: Hee-Jeong_Sampen@rush.edu.
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Im
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, United States; Department of Biochemistry & Molecular Biology, Mayo Clinic, Rochester, MN, United States; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States. Electronic address: vanwijnen.andre@mayo.edu.
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
mesh_terms: D000368:Aged; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007596:Joints / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017423:Sequence Analysis, RNA
keywords: Cartilage; Cell adhesion; Collins grade; ECM; Galaxy