Meniscus beyond mechanics: Using biology to advance our understanding of meniscus injury and treatment

Farooq, Muhammad; McNulty, Amy L.

doi:10.1080/03008207.2017.1312921

Cited by 12 publications

(11 citation statements)

References 15 publications

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“…In addition, GAG content in IL-1β-treated menisci decreased significantly compared with controls. These findings are consistent with those reported for osteoarthritic knees with degenerative menisci [13][14][15] and have important clinical implications for nonsurgical treatment of these patients.…”

Section: Discussionsupporting

confidence: 90%

“…11,12 Among the types of meniscal pathology, the degenerative meniscus, in particular, has received attention recently with respect to its roles in knee health and function with a focus on the merits of nonoperative treatment. [13][14][15][16] Therefore, understanding the mechanisms for meniscal degeneration and the associated contributions to OA development and progression is vital to determining optimal treatments for meniscal pathology in patients.…”

mentioning

confidence: 99%

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Metabolic Responses of Meniscus to IL-1β

Cook

Stoker

2018

J Knee Surg

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This article identifies the potential mechanisms of action for meniscal degeneration in response to joint inflammation and potential contributions of the meniscus to the development and progression of osteoarthritis (OA). It was hypothesized that interleukin-1β (IL-1β) stimulation of meniscal explants would result in significant increases in nitric oxide (NO), matrix metalloproteinase (MMP) production and activity, and relevant cytokine production compared with controls. Canine meniscal explants (4 mm) were cultured for 21 days with (IL-1) or without (negative control [NC]) 50 ng/mL rcIL-1β ( = 6/group). Media were changed every 3 days and analyzed for MMP activity, ADAMTS-4 activity, MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, NO, prostaglandin E (PGE2), IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1), and keratinocyte-derived chemokine (KC) concentrations. Media NO and PGE2 concentrations were significantly higher in the IL-1 group at all time points except for days 9 and 12. The concentrations of MMP-13 were significantly higher in the IL-1 group at days 3, 6, 9, and 12. The production of MMP-2 was significantly lower in the IL-1 group on days 3 through 15. ADAMTS4 activity was significantly higher in the IL-1 group on days 6 through 18. MMP-3 concentrations and general MMP activity were significantly higher in the IL-1 group at all time points. Concentrations of IL-6, IL-8, MCP-1, and KC were significantly higher in the IL-1 group at most time points. Glycosaminoglycans (GAG) content decreased significantly ( = 0.009) in the IL-1 group compared with the NC group. Proinflammatory mediators appear to directly influence degradative processes in the meniscus, which in turn contribute to development and progression of OA by production of proinflammatory and degradative mediators. These findings have important clinical implications for the management of the degenerative meniscus and the osteoarthritic knee.

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

Metabolic Responses of Meniscus to IL-1β

Cook

Stoker

2018

J Knee Surg

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“…These studies are insightful as to different forms of OA which develop following meniscal or ligament injury [66]. The use of animal meniscal models [43,67,68,69,70] have also contributed significantly to a greater understanding of the pathobiology of meniscal degeneration and traumatic meniscal injury and may aid in the formulation of therapeutic interventions on these meniscal tissues [71,72].…”

Section: Studies On Meniscal Tissues In Health and Diseasementioning

confidence: 99%

“…Many reviews have emphasized the great potential of MSCs for meniscal repair applications [25,31,36,40,42,43,45,71]. MSCs have been employed in numerous strategies aimed to promote repair of meniscal lacerations [23] and defects in the avascular inner meniscal zone [39,89,90,91] or in meniscal replacement in meniscectomised animals [83].…”

Section: Current Approaches In Meniscal Repairmentioning

confidence: 99%

The Importance of the Knee Joint Meniscal Fibrocartilages as Stabilizing Weight Bearing Structures Providing Global Protection to Human Knee-Joint Tissues

Melrose

2019

Cells

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The aim of this study was to review aspects of the pathobiology of the meniscus in health and disease and show how degeneration of the meniscus can contribute to deleterious changes in other knee joint components. The menisci, distinctive semilunar weight bearing fibrocartilages, provide knee joint stability, co-ordinating functional contributions from articular cartilage, ligaments/tendons, synovium, subchondral bone and infra-patellar fat pad during knee joint articulation. The meniscus contains metabolically active cell populations responsive to growth factors, chemokines and inflammatory cytokines such as interleukin-1 and tumour necrosis factor-alpha, resulting in the synthesis of matrix metalloproteases and A Disintegrin and Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS)-4 and 5 which can degrade structural glycoproteins and proteoglycans leading to function-limiting changes in meniscal and other knee joint tissues. Such degradative changes are hall-marks of osteoarthritis (OA). No drugs are currently approved that change the natural course of OA and translate to long-term, clinically relevant benefits. For any pharmaceutical therapeutic intervention in OA to be effective, disease modifying drugs will have to be developed which actively modulate the many different cell types present in the knee to provide a global therapeutic. Many individual and combinatorial approaches are being developed to treat or replace degenerate menisci using 3D printing, bioscaffolds and hydrogel delivery systems for therapeutic drugs, growth factors and replacement progenitor cell populations recognising the central role the menisci play in knee joint health.

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“…Several studies have investigated altered knee biomechanics after ACL [8][9][10][11][12][13] and meniscus injuries [14][15][16][17][18], suggesting possible associations with PTOA. Other studies suggest that biological changes [19][20][21][22][23][24] that occur within the joint following injury may play a role in PTOA development as well. Nonetheless, there is little data on the biochemical and cellular environment of the joint following injury.…”

Section: Introductionmentioning

confidence: 99%

Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries

et al. 2021

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Background Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joints at the time of ACL and meniscal surgeries. Methods Twenty-nine patients (14 meniscus-injured and 15 ACL-injured) undergoing ACL and/or meniscus surgery but with a normal contralateral knee were recruited. During surgery, synovial fluid was aspirated from both normal and injured knees. Synovial fluid cells were pelleted, washed, and stained with an antibody cocktail consisting of fluorescent antibodies for cell surface proteins. Analysis of immune cells in the synovial fluid was performed by polychromatic flow cytometry. A broad spectrum immune cell panel was used in the first 10 subjects. Based on these results, a T cell-specific panel was used in the subsequent 19 subjects. Results Using the broad spectrum immune cell panel, we detected significantly more total viable cells and CD3 T cells in the injured compared to the paired normal knees. In addition, there were significantly more injured knees with T cells above a 500-cell threshold. Within the injured knees, CD4 and CD8 T cells were able to be differentiated into subsets. The frequency of total CD4 T cells was significantly different among injury types, but no statistical differences were detected among CD4 and CD8 T cell subsets by injury type. Conclusions Our findings provide foundational data showing that ACL and meniscus injuries induce an immune cell-rich microenvironment that consists primarily of T cells with multiple T helper phenotypes. Future studies investigating the relationship between immune cells and joint degeneration may provide an enhanced understanding of the pathophysiology of PTOA following joint injury.

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Meniscus beyond mechanics: Using biology to advance our understanding of meniscus injury and treatment

Cited by 12 publications

References 15 publications

Metabolic Responses of Meniscus to IL-1β

Metabolic Responses of Meniscus to IL-1β

The Importance of the Knee Joint Meniscal Fibrocartilages as Stabilizing Weight Bearing Structures Providing Global Protection to Human Knee-Joint Tissues

Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries

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