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Updated: Sep 3, 2025

Tissue Collection and RNA Extraction from the Human Osteoarthritic Knee Joint
Published on: July 22, 2021
Association of circulating gene expression signatures with stiffness following total knee arthroplasty for
Meghan A Kirksey1,2,3, Samantha G Lessard1,4,5, Marjan Khan1,4,5
1Hospital for Special Surgery, New York, NY, 10021, USA.
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.
Insights
Patients undergoing total knee arthroplasty (TKA) may develop stiffness due to altered gene expression. This study identified perioperative blood gene signatures associated with early knee range of motion outcomes after TKA.
Area of Science:
- Orthopedic Surgery
- Immunology
- Genomics
Background:
- A subset of total knee arthroplasty (TKA) patients experience debilitating knee stiffness post-surgery.
- The underlying causes of this stiffness, particularly dysregulated immune and inflammatory responses and their gene signatures, remain poorly understood.
- Current limitations hinder the identification of at-risk patients and the development of preventative strategies for poor surgical outcomes.
Purpose of the Study:
- To identify perioperative blood gene expression signatures in patients undergoing TKA for knee osteoarthritis.
- To investigate the association between these gene signatures and early surgical outcomes, specifically knee range of motion (ROM).
Main Methods:
- Pilot study integrating clinical outcomes (6 weeks post-surgery) with transcriptomics of blood samples.
- Blood samples were collected immediately before surgery and 24 hours after surgery.
- Analysis focused on identifying gene expression differences between patients with and without stiffness.
Main Results:
- Patients who developed knee stiffness at 6 weeks post-TKA exhibited a more variable and attenuated circulating gene expression response immediately after surgery.
- Distinct gene expression patterns were observed in the peripheral blood of patients who later developed stiffness.
Conclusions:
- Perioperative gene expression signatures in peripheral blood may serve as early indicators of TKA-associated knee stiffness.
- These findings suggest potential biomarkers for identifying patients at risk of poor ROM outcomes after TKA.
- Further research into these gene signatures could inform preventative interventions for TKA patients.
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