Pilon Fractures: An Ideal Model to Understand Biological Factors Implicated in the Pathogenesis of Posttraumatic Osteoarthritis

Category: Ankle Arthritis; Trauma Introduction/Purpose: Intraarticular pilon fractures have a high rate of posttraumatic osteoarthritis (PTOA) despite anatomic reduction of the articular surface. Elevated synovial inflammatory proteins triggered by injury contribute to PTOA development.MicroRNAs (mi...

Full description

Saved in:
Bibliographic Details
Main Authors: Jeffrey A. Foster MD, Jarod T. Griffin MD, Maaz Muhammad MD, Carlos R. Sierra-Arce MS, Wyatt G.S. Southall BS, Jacob S.W. Borgida BS, Robert K. Wagner MD, Ahmed Ismaeel PhD, John J. McCarthy PhD, Thuan V. Ly MD, Arjun Srinath MD, MPH, David C. Landy MD, PhD, Arun Aneja MD, PhD
Format: Article
Language:English
Published: SAGE Publishing 2024-12-01
Series:Foot & Ankle Orthopaedics
Online Access:https://doi.org/10.1177/2473011424S00432
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850059743982256128
author Jeffrey A. Foster MD
Jarod T. Griffin MD
Maaz Muhammad MD
Carlos R. Sierra-Arce MS
Wyatt G.S. Southall BS
Jacob S.W. Borgida BS
Robert K. Wagner MD
Ahmed Ismaeel PhD
John J. McCarthy PhD
Thuan V. Ly MD
Arjun Srinath MD, MPH
David C. Landy MD, PhD
Arun Aneja MD, PhD
author_facet Jeffrey A. Foster MD
Jarod T. Griffin MD
Maaz Muhammad MD
Carlos R. Sierra-Arce MS
Wyatt G.S. Southall BS
Jacob S.W. Borgida BS
Robert K. Wagner MD
Ahmed Ismaeel PhD
John J. McCarthy PhD
Thuan V. Ly MD
Arjun Srinath MD, MPH
David C. Landy MD, PhD
Arun Aneja MD, PhD
author_sort Jeffrey A. Foster MD
collection DOAJ
description Category: Ankle Arthritis; Trauma Introduction/Purpose: Intraarticular pilon fractures have a high rate of posttraumatic osteoarthritis (PTOA) despite anatomic reduction of the articular surface. Elevated synovial inflammatory proteins triggered by injury contribute to PTOA development.MicroRNAs (miRNA), regulators of gene expression, are dysregulated in the cartilage of osteoarthritic joints, and their modulation may deter cartilage destruction. Specifically, miRNA-146a is associated with normal cartilage development and prevents overexpression of inflammatory proteins in degenerative osteoarthritis but is yet to be studied in clinical PTOA. This novel study aims to determine the effect of acute intraarticular pilon fracture on miRNA-146a expression and its association with inflammatory proteins. Methods: Bilateral ankles of patients with unilateral pilon fracture were aspirated for synovial fluid at the time of external fixation and/or open reduction internal fixation (ORIF). After processing, synovial fluid samples were sequenced for small RNA analysis. Measured levels of miRNA-146a in injured ankles were compared to the contralateral uninjured ankles, which served as baseline controls. Results: Five patients with unilateral pilon fractures consented to participate in the study. miRNA-146a was readily detectable in all patient samples. Using uninjured ankles (n=5) as a control, mean fold miRNA-146a expression was 1.0 ±0.93 [Mean ± Standard Deviation (SD)]. In comparison, mean fold miRNA-146a in injured ankles (n=5) was 0.4 ± 0.53(p=0.07). Additional results will be analyzed and available to present at the 2024 AOFAS Annual Meeting. Conclusion: Though not statistically significant, our preliminary data demonstrated that miRNA-146a was lower in injured ankles when compared to uninjured ankles. This study aims to better characterize the effect of acute pilon fracture on miRNA-146 expression and its association with inflammatory proteins. Anticipated results will help elucidate the role of miRNA-146a in the pathogenesis of PTOA following pilon fracture, impacting future PTOA research on the diagnostic and therapeutic capabilities of miRNAs.
format Article
id doaj-art-e10bd2c4dd1c4e629198298561deff12
institution DOAJ
issn 2473-0114
language English
publishDate 2024-12-01
publisher SAGE Publishing
record_format Article
series Foot & Ankle Orthopaedics
spelling doaj-art-e10bd2c4dd1c4e629198298561deff122025-08-20T02:50:48ZengSAGE PublishingFoot & Ankle Orthopaedics2473-01142024-12-01910.1177/2473011424S00432Pilon Fractures: An Ideal Model to Understand Biological Factors Implicated in the Pathogenesis of Posttraumatic OsteoarthritisJeffrey A. Foster MDJarod T. Griffin MDMaaz Muhammad MDCarlos R. Sierra-Arce MSWyatt G.S. Southall BSJacob S.W. Borgida BSRobert K. Wagner MDAhmed Ismaeel PhDJohn J. McCarthy PhDThuan V. Ly MDArjun Srinath MD, MPHDavid C. Landy MD, PhDArun Aneja MD, PhDCategory: Ankle Arthritis; Trauma Introduction/Purpose: Intraarticular pilon fractures have a high rate of posttraumatic osteoarthritis (PTOA) despite anatomic reduction of the articular surface. Elevated synovial inflammatory proteins triggered by injury contribute to PTOA development.MicroRNAs (miRNA), regulators of gene expression, are dysregulated in the cartilage of osteoarthritic joints, and their modulation may deter cartilage destruction. Specifically, miRNA-146a is associated with normal cartilage development and prevents overexpression of inflammatory proteins in degenerative osteoarthritis but is yet to be studied in clinical PTOA. This novel study aims to determine the effect of acute intraarticular pilon fracture on miRNA-146a expression and its association with inflammatory proteins. Methods: Bilateral ankles of patients with unilateral pilon fracture were aspirated for synovial fluid at the time of external fixation and/or open reduction internal fixation (ORIF). After processing, synovial fluid samples were sequenced for small RNA analysis. Measured levels of miRNA-146a in injured ankles were compared to the contralateral uninjured ankles, which served as baseline controls. Results: Five patients with unilateral pilon fractures consented to participate in the study. miRNA-146a was readily detectable in all patient samples. Using uninjured ankles (n=5) as a control, mean fold miRNA-146a expression was 1.0 ±0.93 [Mean ± Standard Deviation (SD)]. In comparison, mean fold miRNA-146a in injured ankles (n=5) was 0.4 ± 0.53(p=0.07). Additional results will be analyzed and available to present at the 2024 AOFAS Annual Meeting. Conclusion: Though not statistically significant, our preliminary data demonstrated that miRNA-146a was lower in injured ankles when compared to uninjured ankles. This study aims to better characterize the effect of acute pilon fracture on miRNA-146 expression and its association with inflammatory proteins. Anticipated results will help elucidate the role of miRNA-146a in the pathogenesis of PTOA following pilon fracture, impacting future PTOA research on the diagnostic and therapeutic capabilities of miRNAs.https://doi.org/10.1177/2473011424S00432
spellingShingle Jeffrey A. Foster MD
Jarod T. Griffin MD
Maaz Muhammad MD
Carlos R. Sierra-Arce MS
Wyatt G.S. Southall BS
Jacob S.W. Borgida BS
Robert K. Wagner MD
Ahmed Ismaeel PhD
John J. McCarthy PhD
Thuan V. Ly MD
Arjun Srinath MD, MPH
David C. Landy MD, PhD
Arun Aneja MD, PhD
Pilon Fractures: An Ideal Model to Understand Biological Factors Implicated in the Pathogenesis of Posttraumatic Osteoarthritis
Foot & Ankle Orthopaedics
title Pilon Fractures: An Ideal Model to Understand Biological Factors Implicated in the Pathogenesis of Posttraumatic Osteoarthritis
title_full Pilon Fractures: An Ideal Model to Understand Biological Factors Implicated in the Pathogenesis of Posttraumatic Osteoarthritis
title_fullStr Pilon Fractures: An Ideal Model to Understand Biological Factors Implicated in the Pathogenesis of Posttraumatic Osteoarthritis
title_full_unstemmed Pilon Fractures: An Ideal Model to Understand Biological Factors Implicated in the Pathogenesis of Posttraumatic Osteoarthritis
title_short Pilon Fractures: An Ideal Model to Understand Biological Factors Implicated in the Pathogenesis of Posttraumatic Osteoarthritis
title_sort pilon fractures an ideal model to understand biological factors implicated in the pathogenesis of posttraumatic osteoarthritis
url https://doi.org/10.1177/2473011424S00432
work_keys_str_mv AT jeffreyafostermd pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis
AT jarodtgriffinmd pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis
AT maazmuhammadmd pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis
AT carlosrsierraarcems pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis
AT wyattgssouthallbs pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis
AT jacobswborgidabs pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis
AT robertkwagnermd pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis
AT ahmedismaeelphd pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis
AT johnjmccarthyphd pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis
AT thuanvlymd pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis
AT arjunsrinathmdmph pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis
AT davidclandymdphd pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis
AT arunanejamdphd pilonfracturesanidealmodeltounderstandbiologicalfactorsimplicatedinthepathogenesisofposttraumaticosteoarthritis