Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study

TKAF Consortium

doi:10.1038/s41598-022-16868-y

Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study

TKAF Consortium

Hospital for Special Surgery

Research output: Contribution to journal › Article › peer-review

Abstract

A subset of patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis develop debilitating knee stiffness (reduced range of motion) for poorly understood reasons. Dysregulated inflammatory and immune responses to surgery correlate with reduced surgical outcomes, but the dysregulated gene signatures in patients with stiffness after TKA are poorly defined. As a consequence, we are limited in our ability to identify patients at risk of developing poor surgical outcomes and develop preventative approaches. In this pilot study we aimed to identify perioperative blood gene signatures in patients undergoing TKA for knee osteoarthritis and its association with early surgical outcomes, specifically knee range of motion. To do this, we integrated clinical outcomes collected at 6 weeks after surgery with transcriptomics analyses in blood samples collected immediately before surgery and at 24 h after surgery. We found that patients with stiffness at 6 weeks after surgery have a more variable and attenuated circulating gene expression response immediately after surgery. Our results suggest that patients with stiffness following TKA may have distinct gene expression signatures detectable in peripheral blood in the immediate postoperative period.

Original language	English
Article number	12651
Journal	Scientific Reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-16868-y
Publication status	Published - Dec 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

Funding

The authors are also grateful to the Tow Foundation, which provided support for the David Z. Rosensweig Genomics Research Center, Giammaria Giuliani, the Ira W. DeCamp Foundation, and the Ambrose Monell Foundation. Technical support was provided by the Epigenomics Core of Weill Cornell Medicine. This work was supported by an Adult Reconstruction and Joint Replacement Marmor Research Award (M.A.K.), Young Investigator Award, and Research and Education Fund grant from the HSS Department of Anesthesiology, Critical Care, and Pain Management (M.A.K), and a gift from Marina Kellen French and the Anna-Maria and Stephen Kellen French Foundation. Research reported in this publication was also supported by the National Center For Advancing Translational Science of the National Institute of Health Under Award Number UL1TR002384.

Funders	Funder number
Stephen Kellen French Foundation
National Institutes of Health
Ambrose Monell Foundation
National Center for Advancing Translational Sciences	UL1TR002384
Ira W. DeCamp Foundation
Department of Anesthesiology, Medical College of Wisconsin
Tow Foundation

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Cite this

@article{53a9825e42a440b289352cc1fbe790c8,

title = "Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study",

abstract = "A subset of patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis develop debilitating knee stiffness (reduced range of motion) for poorly understood reasons. Dysregulated inflammatory and immune responses to surgery correlate with reduced surgical outcomes, but the dysregulated gene signatures in patients with stiffness after TKA are poorly defined. As a consequence, we are limited in our ability to identify patients at risk of developing poor surgical outcomes and develop preventative approaches. In this pilot study we aimed to identify perioperative blood gene signatures in patients undergoing TKA for knee osteoarthritis and its association with early surgical outcomes, specifically knee range of motion. To do this, we integrated clinical outcomes collected at 6 weeks after surgery with transcriptomics analyses in blood samples collected immediately before surgery and at 24 h after surgery. We found that patients with stiffness at 6 weeks after surgery have a more variable and attenuated circulating gene expression response immediately after surgery. Our results suggest that patients with stiffness following TKA may have distinct gene expression signatures detectable in peripheral blood in the immediate postoperative period.",

author = "{TKAF Consortium} and Kirksey, {Meghan A.} and Lessard, {Samantha G.} and Marjan Khan and Birch, {George A.} and David Oliver and Purva Singh and Valeria Rotundo and Alexandra Sideris and Tania Pannellini and Nocon, {Allina A.} and Mark Youseff and Paul Guirguis and Bauer, {Thomas W.} and Bogner, {Eric A.} and Bostrom, {Mathias P.} and Haas, {Steven B.} and Jules-Elysee, {Kethy M.} and Figgie, {Mark P.} and Mayman, {David J.} and McLawhorn, {Alexander S.} and Cross, {Michael B.} and Padgett, {Douglas E.} and Pernis, {Alessandra B.} and Rodeo, {Scott A.} and Kathleen Tam and Westrich, {Geoffrey H.} and Potter, {Hollis G.} and Koff, {Matthew F.} and Ivashkiv, {Lionel B.} and Sculco, {Thomas P.} and Wright, {Timothy M.} and {Gonzalez Della Valle}, Alejandro and Parks, {Michael L.} and Sculco, {Peter K.} and Miguel Otero",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41598-022-16868-y",

language = "English",

volume = "12",

journal = "Scientific Reports",

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T1 - Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis

T2 - a pilot study

AU - TKAF Consortium

AU - Kirksey, Meghan A.

AU - Lessard, Samantha G.

AU - Khan, Marjan

AU - Birch, George A.

AU - Oliver, David

AU - Singh, Purva

AU - Rotundo, Valeria

AU - Sideris, Alexandra

AU - Pannellini, Tania

AU - Nocon, Allina A.

AU - Youseff, Mark

AU - Guirguis, Paul

AU - Bauer, Thomas W.

AU - Bogner, Eric A.

AU - Bostrom, Mathias P.

AU - Haas, Steven B.

AU - Jules-Elysee, Kethy M.

AU - Figgie, Mark P.

AU - Mayman, David J.

AU - McLawhorn, Alexander S.

AU - Cross, Michael B.

AU - Padgett, Douglas E.

AU - Pernis, Alessandra B.

AU - Rodeo, Scott A.

AU - Tam, Kathleen

AU - Westrich, Geoffrey H.

AU - Potter, Hollis G.

AU - Koff, Matthew F.

AU - Ivashkiv, Lionel B.

AU - Sculco, Thomas P.

AU - Wright, Timothy M.

AU - Gonzalez Della Valle, Alejandro

AU - Parks, Michael L.

AU - Sculco, Peter K.

AU - Otero, Miguel

PY - 2022/12

Y1 - 2022/12

N2 - A subset of patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis develop debilitating knee stiffness (reduced range of motion) for poorly understood reasons. Dysregulated inflammatory and immune responses to surgery correlate with reduced surgical outcomes, but the dysregulated gene signatures in patients with stiffness after TKA are poorly defined. As a consequence, we are limited in our ability to identify patients at risk of developing poor surgical outcomes and develop preventative approaches. In this pilot study we aimed to identify perioperative blood gene signatures in patients undergoing TKA for knee osteoarthritis and its association with early surgical outcomes, specifically knee range of motion. To do this, we integrated clinical outcomes collected at 6 weeks after surgery with transcriptomics analyses in blood samples collected immediately before surgery and at 24 h after surgery. We found that patients with stiffness at 6 weeks after surgery have a more variable and attenuated circulating gene expression response immediately after surgery. Our results suggest that patients with stiffness following TKA may have distinct gene expression signatures detectable in peripheral blood in the immediate postoperative period.

AB - A subset of patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis develop debilitating knee stiffness (reduced range of motion) for poorly understood reasons. Dysregulated inflammatory and immune responses to surgery correlate with reduced surgical outcomes, but the dysregulated gene signatures in patients with stiffness after TKA are poorly defined. As a consequence, we are limited in our ability to identify patients at risk of developing poor surgical outcomes and develop preventative approaches. In this pilot study we aimed to identify perioperative blood gene signatures in patients undergoing TKA for knee osteoarthritis and its association with early surgical outcomes, specifically knee range of motion. To do this, we integrated clinical outcomes collected at 6 weeks after surgery with transcriptomics analyses in blood samples collected immediately before surgery and at 24 h after surgery. We found that patients with stiffness at 6 weeks after surgery have a more variable and attenuated circulating gene expression response immediately after surgery. Our results suggest that patients with stiffness following TKA may have distinct gene expression signatures detectable in peripheral blood in the immediate postoperative period.

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DO - 10.1038/s41598-022-16868-y

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SN - 2045-2322

VL - 12

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 12651

ER -

Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study

Abstract

Bibliographical note

Funding

ASJC Scopus Subject Areas

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