Interleukin-1 and tumor necrosis factor alpha inhibit repair of the porcine meniscus in vitro

Hennerbichler, Alfred; Moutos, Franklin T.; Hennerbichler, Diana; Weinberg, J. Brice; Guilak, Farshid

doi:10.1016/j.joca.2007.03.003

Cited by 65 publications

(82 citation statements)

References 54 publications

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“…We used an explant model system described previously (19,34) to study integrative repair of the meniscus. Medial menisci were harvested from the knees of 2-3-year-old skeletally mature female pigs; tissues were obtained from a local abattoir.…”

Section: Methodsmentioning

confidence: 99%

“…Similarly, TNF␣ increases the production of nitric oxide (29) and inhibits the synthesis of proteoglycans in meniscal cells and explants (26,33). These catabolic and antianabolic effects of IL-1 and TNF␣ have been shown to inhibit the repair of meniscal lesions when present at very high concentrations (34). However, the long-term effects of lower, physiologically relevant concentrations of these cytokines on meniscal repair are not known.…”

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confidence: 99%

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Enhanced integrative repair of the porcine meniscus in vitro by inhibition of interleukin‐1 or tumor necrosis factor α

McNulty

Moutos

Weinberg

et al. 2007

Arthritis & Rheumatism

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Objective. To examine the hypotheses that increasing concentrations of interleukin-1 (IL-1) or tumor necrosis factor ␣ (TNF␣) inhibit the integrative repair of the knee meniscus in an in vitro model system, and that inhibitors of these cytokines will enhance repair.Methods. Explants (8 mm in diameter) were harvested from porcine medial menisci. To simulate a full-thickness defect, a 4-mm-diameter core was removed and reinserted. Explants were cultured for 14, 28, or 42 days in the presence of 0-1,000 pg/ml of IL-1 or TNF␣. Explants were also cultured in the presence of IL-1 or TNF␣ with IL-1 receptor antagonist (IL-1Ra) or TNF monoclonal antibody (mAb). At the end of the culture period, biomechanical testing, cell viability, and histologic analyses were performed to quantify the extent of repair.Results. Mechanical testing revealed increased repair strength, cell accumulation, and tissue formation at the interface over time under control conditions. Pathophysiologic concentrations of both IL-1 and TNF␣ significantly decreased repair strength, cell migration, and tissue formation at the interface. The addition of IL-1Ra or TNF mAb to explants prevented the effects of IL-1 or TNF␣, respectively. Conclusion. Our findings document that physiologically relevant concentrations of IL-1 and TNF␣ inhibit meniscal repair in vitro and therefore may also inhibit meniscal repair during arthritis or following joint injury. The finding that IL-1Ra and TNF mAb promoted integrative meniscal repair in an inflammatory microenvironment suggests that intraarticular delivery of IL-1Ra and/or TNF mAb may be useful clinically to promote meniscal healing following injury.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Enhanced integrative repair of the porcine meniscus in vitro by inhibition of interleukin‐1 or tumor necrosis factor α

McNulty

Moutos

Weinberg

et al. 2007

Arthritis & Rheumatism

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“…Specifically, IL-1 increases the expression and activity of MMPs in meniscal cells and explants [11,21,58]. Additionally, IL-1 dose-dependently decreases the interfacial shear strength of meniscal repair, suppresses cell accumulation, and inhibits tissue formation in the meniscal repair interface [24,41]. Of particular interest is the finding that acute exposure of meniscal tissue to IL-1 for only 1 or 3 days is sufficient to suppress tissue repair for up to 4 weeks [58].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Matrix Metalloproteinases Enhances In Vitro Repair of the Meniscus

McNulty

Weinberg

Guilak

2008

Clin Orthop Relat Res

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Damage or injury of the meniscus is associated with onset and progression of knee osteoarthritis (OA). The intrinsic repair capacity of the meniscus is inhibited by inflammatory cytokines, such as interleukin-1 (IL-1). Using an in vitro meniscal repair model system, we examined the hypothesis that inhibition of matrix metalloproteinases (MMPs) in the presence of IL-1 will enhance repair of meniscal lesions. Integrative repair of the meniscus was examined between two concentric explants cultured with IL-1 and various MMP inhibitors for 14 days. Throughout the culture period, we assessed total specific MMP activity in the media. At harvest, biomechanical testing to assess the strength of repair and histologic staining were performed. IL-1 decreased the shear strength of repair, as compared with control explants. In the presence of IL-1, the broad-spectrum MMP inhibitor GM 6001 decreased the MMP activity in the media, increased the shear strength of repair, and enhanced tissue repair in the interface. However, individual MMP inhibitors did not alter the shear strength of repair in either the presence or absence of IL-1. These findings suggest IL-1 may inhibit meniscal repair through upregulation of MMPs, but inhibition of multiple MMPs may be necessary to promote integrative meniscal repair.

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“…Webber et al [31] used meniscal fibrochondrocyte from New Zealand white rabbits to demonstrate a dose-dependent proliferative response in cell cultures to fibroblast growth factor (FGF) and human platelet lysate. With this in mind, other investigators have sought to elucidate the role of various cytokines and growth factors in healing [32,33].…”

Section: Cell Biology and Meniscal Healing: Cytokines And Growth Factorsmentioning

confidence: 99%

“…Hennerbichler et al [32] evaluated the role of such cytokines on healing of full thickness meniscal defects made in a porcine meniscal explant in vitro. Specimens were cultured in 1 of 3 conditions: (1) media alone, (2) media with interleukin-1 (IL-1), or (3) media with tumor necrosis factor alpha (TNF-α).…”

Section: Cell Biology and Meniscal Healing: Cytokines And Growth Factorsmentioning

confidence: 99%

Augmentation techniques for isolated meniscal tears

Taylor

Rodeo

2013

Curr Rev Musculoskelet Med

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Meniscal tears are relatively common injuries sustained by athletes and non-athletes alike and have far reaching functional and financial implications. Studies have clearly demonstrated the important biomechanical role played by the meniscus. Long-term follow-up studies of post-menisectomy patients show a predisposition toward the development of degenerative arthritic changes. As such, substantial efforts have been made by researchers and clinicians to understand the cellular and molecular basis of meniscal healing. Proinflammatory cytokines have been shown to have a catabolic effect on meniscal healing. In vitro and some limited in vivo studies have shown a proliferative and anabolic response to various growth factors. Surgical techniques that have been developed to stimulate a healing response include mechanical abrasion, fibrin clot application, growth factor application, and attempts at meniscal neovascularization. This article discusses various augmentation techniques for meniscal repair and reviews the current literature with regard to fibrin clot, platelet rich plasma, proinflammatory cytokines, and application of growth factors.

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Interleukin-1 and tumor necrosis factor alpha inhibit repair of the porcine meniscus in vitro

Cited by 65 publications

References 54 publications

Enhanced integrative repair of the porcine meniscus in vitro by inhibition of interleukin‐1 or tumor necrosis factor α

Enhanced integrative repair of the porcine meniscus in vitro by inhibition of interleukin‐1 or tumor necrosis factor α

Inhibition of Matrix Metalloproteinases Enhances In Vitro Repair of the Meniscus

Augmentation techniques for isolated meniscal tears

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