TY - JOUR
T1 - Molecular pathology of human knee arthrofibrosis defined by RNA sequencing
AU - Bayram, Banu
AU - Limberg, Afton K.
AU - Salib, Christopher G.
AU - Bettencourt, Jacob W.
AU - Trousdale, William H.
AU - Lewallen, Eric A.
AU - Reina, Nicolas
AU - Paradise, Christopher R.
AU - Thaler, Roman
AU - Morrey, Mark E.
AU - Sanchez-Sotelo, Joaquin
AU - Berry, Daniel J.
AU - van Wijnen, Andre J.
AU - Abdel, Matthew P.
N1 - Funding Information:
We thank all members of our laboratories, including Amel Dudakovic, Ph.D, Viktor Janz, M.D., Aaron R. Owen, M.D., Juan S. Vargas-Hernandez, M.D., and Travis W. Turner, B·S., for their enthusiastic support, stimulating discussions, and/or generous sharing of reagents, data, ideas and protocols. We also appreciate the administrative assistance of Marina S. Ganshina, B·S., and Sandra M. Passe. This study was pursued with the generous philanthropic support of the Anna-Maria and Stephen Kellen Foundation (to M.P.A). This work was also supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number R01 AR072597 (to M.P.A). Auxiliary support was provided by R01 AR049069 (to A.J.v.W) and the William H. and Karen J. Eby Foundation (to A.J.v.W). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health .
Funding Information:
We thank all members of our laboratories, including Amel Dudakovic, Ph.D, Viktor Janz, M.D. Aaron R. Owen, M.D. Juan S. Vargas-Hernandez, M.D. and Travis W. Turner, B·S. for their enthusiastic support, stimulating discussions, and/or generous sharing of reagents, data, ideas and protocols. We also appreciate the administrative assistance of Marina S. Ganshina, B·S. and Sandra M. Passe. This study was pursued with the generous philanthropic support of the Anna-Maria and Stephen Kellen Foundation (to M.P.A). This work was also supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number R01 AR072597 (to M.P.A). Auxiliary support was provided by R01 AR049069 (to A.J.v.W) and the William H. and Karen J. Eby Foundation (to A.J.v.W). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/7
Y1 - 2020/7
N2 - Arthrofibrosis is an abnormal histopathologic response, is debilitating for patients, and poses a substantial unsolved clinical challenge. This study characterizes molecular biomarkers and regulatory pathways associated with arthrofibrosis by comparing fibrotic and non-fibrotic human knee tissue. The fibrotic group encompasses 4 patients undergoing a revision total knee arthroplasty (TKA) for arthrofibrosis (RTKA-A) while the non-fibrotic group includes 4 patients undergoing primary TKA for osteoarthritis (PTKA) and 4 patients undergoing revision TKA for non-arthrofibrotic and non-infectious etiologies (RTKA-NA). RNA-sequencing of posterior capsule specimens revealed differences in gene expression between each patient group by hierarchical clustering, principal component analysis, and correlation analyses. Multiple differentially expressed genes (DEGs) were defined in RTKA-A versus PTKA patients (i.e., 2059 up-regulated and 1795 down-regulated genes) and RTKA-A versus RTKA-NA patients (i.e., 3255 up-regulated and 3683 down-regulated genes). Our findings define molecular and pathological markers of arthrofibrosis, as well as novel potential targets for risk profiling, early diagnosis and pharmacological treatment of patients.
AB - Arthrofibrosis is an abnormal histopathologic response, is debilitating for patients, and poses a substantial unsolved clinical challenge. This study characterizes molecular biomarkers and regulatory pathways associated with arthrofibrosis by comparing fibrotic and non-fibrotic human knee tissue. The fibrotic group encompasses 4 patients undergoing a revision total knee arthroplasty (TKA) for arthrofibrosis (RTKA-A) while the non-fibrotic group includes 4 patients undergoing primary TKA for osteoarthritis (PTKA) and 4 patients undergoing revision TKA for non-arthrofibrotic and non-infectious etiologies (RTKA-NA). RNA-sequencing of posterior capsule specimens revealed differences in gene expression between each patient group by hierarchical clustering, principal component analysis, and correlation analyses. Multiple differentially expressed genes (DEGs) were defined in RTKA-A versus PTKA patients (i.e., 2059 up-regulated and 1795 down-regulated genes) and RTKA-A versus RTKA-NA patients (i.e., 3255 up-regulated and 3683 down-regulated genes). Our findings define molecular and pathological markers of arthrofibrosis, as well as novel potential targets for risk profiling, early diagnosis and pharmacological treatment of patients.
KW - Acquired idiopathic stiffness
KW - DEGs
KW - Joint stiffness
KW - RNA-seq
KW - Total knee Arthroplasty
UR - http://www.scopus.com/inward/record.url?scp=85081549963&partnerID=8YFLogxK
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U2 - 10.1016/j.ygeno.2020.03.004
DO - 10.1016/j.ygeno.2020.03.004
M3 - Review article
C2 - 32145378
AN - SCOPUS:85081549963
SN - 0888-7543
VL - 112
SP - 2703
EP - 2712
JO - Genomics
JF - Genomics
IS - 4
ER -