Tibiofemoral articular cartilage composition differs based on serum biochemical profiles following anterior cruciate ligament reconstruction

Lisee, Caroline; Spang, Jeffrey T.; Loeser, Richard F.; Longobardi, Lara; Lalush, David S.; Nissman, Daniel; Schwartz, Todd A.; Hu, David; Pietrosimone, Brian

doi:10.1016/j.joca.2021.09.005

Cited by 11 publications

(8 citation statements)

References 44 publications

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“…Rabbits were euthanized at 1-, 3- or 6-months post-trauma, with n = 6 in each time-point group. These timepoints were chosen to correspond to what others have done in the literature studying PTOA ( Coleman et al, 2018 ; Lisee et al, 2021 ). Based on our previous studies using this animal model, and evaluation of mechanical properties of the cartilage and meniscus, an n = 6 in each group provides 80% power in the study ( Narez et al, 2021a ; Wei et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

A Morphological Study of the Meniscus, Cartilage and Subchondral Bone Following Closed-Joint Traumatic Impact to the Knee

Donahue

Narez

Powers

et al. 2022

Front. Bioeng. Biotechnol.

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Post-traumatic osteoarthritis (PTOA) is a debilitating disease that is a result of a breakdown of knee joint tissues following traumatic impact. The interplay of how these tissues influence each other has received little attention because of complex interactions. This study was designed to correlate the degeneration of the menisci, cartilage and subchondral bone following an acute traumatic event that resulted in anterior cruciate ligament (ACL) and medial meniscus tears. We used a well-defined impact injury animal model that ruptures the ACL and tears the menisci. Subsequently, the knee joints underwent ACL reconstruction and morphological analyses were performed on the menisci, cartilage and subchondral bone at 1-, 3- and 6-months following injury. The results showed that the morphological scores of the medial and lateral menisci worsened with time, as did the tibial plateau and femoral condyle articular cartilage scores. The medial meniscus was significantly correlated to the medial tibial subchondral bone at 1 month (p = 0.01), and to the medial tibial cartilage at 3 months (p = 0.04). There was only one significant correlation in the lateral hemijoint, i.e., the lateral tibial cartilage to the lateral tibial subchondral bone at 6 months (p = 0.05). These data may suggest that, following trauma, the observed medial meniscal damage should be treated acutely by means other than a full or partial meniscectomy, since that procedure may have been the primary cause of degenerative changes in the underlying cartilage and subchondral bone. In addition to potentially treating meniscal damage differently, improvements could be made in optimizing treatment of acute knee trauma.

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Section: Methodsmentioning

confidence: 99%

A Morphological Study of the Meniscus, Cartilage and Subchondral Bone Following Closed-Joint Traumatic Impact to the Knee

Donahue

Narez

Powers

et al. 2022

Front. Bioeng. Biotechnol.

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“…However, the relevance of the CCL2/CCR2 axis for potential PTOA therapies is not limited to mediating the inflammatory response accompanying disease progression but rather, unlike other biomarkers, is directly linked to cartilage and bone integrity, addressing the multitissue aspect of the disease. In addition to macrophages, CCR2 and CCL2 are expressed on chondrocytes, osteoblasts, and tendon fibroblasts, where they exert an important role in early tissue degeneration following injury [ 8 , 12 ]. Our data obtained in human primary chondrocyte cultures demonstrated a temporal action of CCL2 on the expression of its own Ccr2 receptor as well as on cartilage degradation markers (such as MMP1, MMP3, MMP13, and Timp1), activating specific MAP kinases (ERK and p38) and supporting the hypothesis that the CCL2/CCR2 axis might lead to cartilage dysregulation induced by OA [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Sustained inhibition of CC-chemokine receptor-2 via intraarticular deposition of polymeric microplates in post-traumatic osteoarthritis

Özkan

Francesco

Willcockson

et al. 2022

Drug Deliv. and Transl. Res.

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Posttraumatic osteoarthritis (PTOA) is mostly treated via corticosteroid administration, and total joint arthroplasty continues to be the sole effective intervention in severe conditions. To assess the therapeutic potential of CCR2 targeting in PTOA, we used biodegradable microplates (µPLs) to achieve a slow and sustained intraarticular release of the CCR2 inhibitor RS504393 into injured knees and followed joint damage during disease progression. RS504393-loaded µPLs (RS-µPLs) were fabricated via a template-replica molding technique. A mixture of poly(lactic-co-glycolic acid) (PLGA) and RS504393 was deposited into 20 × 10 μm (length × height) wells in a polyvinyl alcohol (PVA) square-patterned template. After physicochemical and toxicological characterizations, the RS504393 release profile from µPL was assessed in PBS buffer. C57BL/6 J male mice were subjected to destabilization of the medial meniscus (DMM)/sham surgery, and RS-µPLs (1 mg/kg) were administered intraarticularly 1 week postsurgery. Administrations were repeated at 4 and 7 weeks post-DMM. Drug free-µPLs (DF-µPLs) and saline injections were performed as controls. Mice were euthanized at 4 and 10 weeks post-DMM, corresponding to the early and severe PTOA stages, respectively. Knees were evaluated for cartilage structure score (ACS, H&E), matrix loss (safranin O score), osteophyte formation and maturation from cartilage to bone (cartilage quantification), and subchondral plate thickness. The RS-µPL architecture ensured the sustained release of CCR2 inhibitors over several weeks, with ~ 20% of RS504393 still available at 21 days. This prolonged release improved cartilage structure and reduced bone damage and synovial hyperplasia at both PTOA stages. Extracellular matrix loss was also attenuated, although with less efficacy. The results indicate that local sustained delivery is needed to optimize CCR2-targeted therapies. Graphical abstract

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“…All assays were performed in duplicate and exhibited < 10% inter‐ and intra‐assay variability. These methods have been described in greater detail previously [18].…”

Section: Methodsmentioning

confidence: 99%

Bone bruising severity after anterior cruciate ligament rupture predicts elevation of chemokine MCP-1 associated with osteoarthritis

et al. 2022

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Purpose Anterior cruciate ligament rupture is associated with characteristic bone contusions in approximately 80% of patients, and these have been correlated with higher pain scores. Bone bruising may indicate joint damage that increases inflammation and the likelihood of posttraumatic osteoarthritis. We sought to characterize the severity of bone bruising following acute anterior cruciate ligament injury and determine if it correlates with synovial fluid and serum levels of the proinflammatory chemokine monocyte chemoattractant protein-1 associated with posttraumatic osteoarthritis. Methods This was a retrospective analysis of data collected prospectively from January 2014 through December 2016. All patients who sustained an acute ligament rupture were evaluated within 15 days of injury, obtained a magnetic resonance imaging study, and underwent bone-patellar-tendon-bone autograft reconstruction were offered enrollment. The overall severity of bone bruising on magnetic resonance imaging was graded (sum of 0–3 grades in 13 sectors of the articular surfaces). Serum and synovial fluid levels of monocyte chemoattractant protein-1 were measured within 14 days of injury, and serum levels were again measured 6 and 12 months following surgery. Separate univariate linear regression models were constructed to determine the association between monocyte chemoattractant protein-1 and bone bruising severity at each time point. Results Forty-eight subjects were included in this study. They had a mean age of 21.4 years and were 48% female. Median overall bone bruising severity was 5 (range 0–14). Severity of bone bruising correlated with higher synovial fluid concentrations of monocyte chemoattractant protein-1 preoperatively (R2 = 0.18, p = 0.009) and with serum concentrations at 12 months post-reconstruction (R2 = 0.12, p = 0.04). Conclusions The severity of bone bruising following anterior cruciate ligament rupture is associated with higher levels of the proinflammatory cytokine monocyte chemoattractant protein-1 in synovial fluid acutely post-injury and in serum 12-months following anterior cruciate ligament reconstruction. This suggests that severe bone bruising on magnetic resonance imaging after ligament rupture may indicate increased risk for persistent joint inflammation and posttraumatic osteoarthritis. Level of evidence III ― retrospective cohort study.

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Tibiofemoral articular cartilage composition differs based on serum biochemical profiles following anterior cruciate ligament reconstruction

Cited by 11 publications

References 44 publications

A Morphological Study of the Meniscus, Cartilage and Subchondral Bone Following Closed-Joint Traumatic Impact to the Knee

A Morphological Study of the Meniscus, Cartilage and Subchondral Bone Following Closed-Joint Traumatic Impact to the Knee

Sustained inhibition of CC-chemokine receptor-2 via intraarticular deposition of polymeric microplates in post-traumatic osteoarthritis

Bone bruising severity after anterior cruciate ligament rupture predicts elevation of chemokine MCP-1 associated with osteoarthritis

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