Inflammatory cytokine levels in synovial fluid 3, 4 days postoperatively and its correlation with early-phase functional recovery after anterior cruciate ligament reconstruction: a cohort study
Abstract:BackgroundSynovial fluid was collected prior to and at 3 to 4 days after ACL reconstruction to investigate the correlation between inflammatory cytokine levels in the acute phase after surgery and physical functional recovery at 3 months postoperatively.Methods For this purpose, 79 patients with ACL reconstruction using semitendinosus tendons were included in the study. Median days from injury to surgery were 80 days (13–291 days). Synovial fluid was obtained just before surgery and at 3 to 4 days after surger… Show more
“…While the acute inflammation phase could be as short as a few days in young animals, 47,48 it can last for weeks in the human knee joint and then be sustained at a lower level for months to years after the initial injury. 4,37 In addition, the longitudinal GAG and collagen loss measured in this study represent the loss of the newly synthesized proteins labeled by click chemistry. Although the data showed the turnover of a subpopulation of total GAG or collagen in the tissue, it enabled the comparisons between different groups and yielded insights into how cytokines and injurious mechanical stresses affect cartilage degradation.…”
During traumatic joint injuries,
impact overloading can cause mechanical
damage to the cartilage. In the following inflammation phase, excessive
inflammatory cytokines (e.g., interleukin-1β
(IL-1β)) can act on chondrocytes, causing over-proliferation,
apoptosis, and extracellular matrix (ECM) degradation that can lead
to osteoarthritis. This study investigated the combined effects of
traumatic overloading and IL-1β challenge on the metabolic activities
of chondrocytes. Bovine cartilage explants underwent impact overloading
followed by IL-1β exposure at a physiologically relevant dosage
(1 ng/mL). New click chemistry-based methods were developed to visualize
and quantify the proliferation of in situ chondrocytes
in a nondestructive manner without the involvement of histological
sectioning or antibodies. Click chemistry-based methods were also
employed to measure the ECM synthesis and degradation in cartilage
explants. As the click reactions are copper-free and bio-orthogonal, i.e., with negligible cellular toxicity, cartilage ECM was
cultured and studied for 6 weeks. Traumatic overloading induced significant
cell death, mainly in the superficial zone. The high number of dead
cells reduced the overall proliferation of chondrocytes as well as
the synthesis of glycosaminoglycan (GAG) and collagen contents, but
overloading alone had no effects on ECM degradation. IL-1β challenge
had little effect on cell viability, proliferation, or protein synthesis
but induced over 40% GAG loss in 10 days and 61% collagen loss in
6 weeks. For the overloaded samples, IL-1β induced greater degrees
of degradation, with 68% GAG loss in 10 days and 80% collagen loss
in 6 weeks. The results imply a necessary immediate ease of inflammation
after joint injuries when trauma damage on cartilage is present. The
new click chemistry methods could benefit many cellular and tissue
engineering studies, providing convenient and sensitive assays of
metabolic activities of cells in native three-dimensional (3D) environments.
“…While the acute inflammation phase could be as short as a few days in young animals, 47,48 it can last for weeks in the human knee joint and then be sustained at a lower level for months to years after the initial injury. 4,37 In addition, the longitudinal GAG and collagen loss measured in this study represent the loss of the newly synthesized proteins labeled by click chemistry. Although the data showed the turnover of a subpopulation of total GAG or collagen in the tissue, it enabled the comparisons between different groups and yielded insights into how cytokines and injurious mechanical stresses affect cartilage degradation.…”
During traumatic joint injuries,
impact overloading can cause mechanical
damage to the cartilage. In the following inflammation phase, excessive
inflammatory cytokines (e.g., interleukin-1β
(IL-1β)) can act on chondrocytes, causing over-proliferation,
apoptosis, and extracellular matrix (ECM) degradation that can lead
to osteoarthritis. This study investigated the combined effects of
traumatic overloading and IL-1β challenge on the metabolic activities
of chondrocytes. Bovine cartilage explants underwent impact overloading
followed by IL-1β exposure at a physiologically relevant dosage
(1 ng/mL). New click chemistry-based methods were developed to visualize
and quantify the proliferation of in situ chondrocytes
in a nondestructive manner without the involvement of histological
sectioning or antibodies. Click chemistry-based methods were also
employed to measure the ECM synthesis and degradation in cartilage
explants. As the click reactions are copper-free and bio-orthogonal, i.e., with negligible cellular toxicity, cartilage ECM was
cultured and studied for 6 weeks. Traumatic overloading induced significant
cell death, mainly in the superficial zone. The high number of dead
cells reduced the overall proliferation of chondrocytes as well as
the synthesis of glycosaminoglycan (GAG) and collagen contents, but
overloading alone had no effects on ECM degradation. IL-1β challenge
had little effect on cell viability, proliferation, or protein synthesis
but induced over 40% GAG loss in 10 days and 61% collagen loss in
6 weeks. For the overloaded samples, IL-1β induced greater degrees
of degradation, with 68% GAG loss in 10 days and 80% collagen loss
in 6 weeks. The results imply a necessary immediate ease of inflammation
after joint injuries when trauma damage on cartilage is present. The
new click chemistry methods could benefit many cellular and tissue
engineering studies, providing convenient and sensitive assays of
metabolic activities of cells in native three-dimensional (3D) environments.
“…Since both inflammation post-injury and the reparative process occur on the order of weeks to months, these prolonging attributes are especially helpful. Delaying meniscal repair procedures after injury, similar to what is done with anterior cruciate ligament reconstruction ( Inoue et al, 2016 ), may help to delay repair until inflammation has subsided, improving the integrative nature, and thus long-term stability, of the repair.…”
Section: Other Joint Factors That Influence Healingmentioning
FIGURE 1 | Meniscus Repair Impediments. (A) Meniscus tears are often classified based on location, orientation, and severity. Location is usually classified by radial axis (inner, intermediate, outer) and circumferential axis (anterior, body, posterior). (B) Meniscus vascularity penetrates only partially into the meniscal body. (C) Circumferential network disruption (radial tears) lead to loss of residual strain, resulting in altered mechano-sensing and potentially cellular apoptosis. (D) Dense extracellular matrix can obstruct repair by limiting cell migration and matrix remodeling. Methods (e.g., growth factors) can improve migration and loosen matrix. (E) Joint factors that influence meniscal repair include concomitant injuries (e.g., ACl, cartilage), inflammation, and varus/valgus loading.
“…A significant negative correlation between the expressions of inflammatory cytokines and knee laxity function score was observed in the patient. The level of IL-1β in the synovial fluid at 3–4 days post-surgery predicted poor functional recovery at 3 months after ACLR ( Inoue et al, 2016 ). In another clinical trial, all patients with tibial tunnel enlargement had elevated synovial levels of TNF-α, IL-6, and NO at 7 days post-operation ( Zysk et al, 2004 ).…”
Section: Role Of Inflammation In Influencing Healing Responsementioning
Anterior cruciate ligament (ACL) tear is common in sports and accidents, and accounts for over 50% of all knee injuries. ACL reconstruction (ACLR) is commonly indicated to restore the knee stability, prevent anterior–posterior translation, and reduce the risk of developing post-traumatic osteoarthritis. However, the outcome of biological graft healing is not satisfactory with graft failure after ACLR. Tendon graft-to-bone tunnel healing and graft mid-substance remodeling are two key challenges of biological graft healing after ACLR. Mounting evidence supports excessive inflammation due to ACL injury and ACLR, and tendon graft-to-bone tunnel motion negatively influences these two key processes. To tackle the problem of biological graft healing, we believe that an inductive approach should be adopted, starting from the endpoint that we expected after ACLR, even though the results may not be achievable at present, followed by developing clinically practical strategies to achieve this ultimate goal. We believe that mineralization of tunnel graft and ligamentization of graft mid-substance to restore the ultrastructure and anatomy of the original ACL are the ultimate targets of ACLR. Hence, strategies that are osteoinductive, angiogenic, or anti-inflammatory should drive graft healing toward the targets. This paper reviews pre-clinical and clinical literature supporting this claim and the role of inflammation in negatively influencing graft healing. The practical considerations when developing a biological therapy to promote ACLR for future clinical translation are also discussed.
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