Abstract
BackgroundJoint inflammation causes meniscus degeneration and can exacerbate post-traumatic meniscus injuries by extracellular matrix degradation, cellular de-differentiation and cell death. The aim of this study was to examine whether anti-inflammatory interleukin-10 exerts protective effects in an in vitro model of TNF-α-induced meniscus degeneration.MethodsMeniscus tissue was harvested from the knees of adult cows. After 24 h of equilibrium explants were simultaneously treated with bovine TNF-α and IL-10. After an incubation time of 72 h cell death was measured histomorphometrically (nuclear blebbing, NB) and release of glycosaminoglycans (GAG, DMMB assay) and nitric oxide (NO, Griess-reagent) were analysed. Transcription levels (mRNA) of matrix degrading enzymes, collagen type X (COL10A1) and nitric oxide synthetase 2 (NOS2) were measured by quantitative real time PCR. TNF-α-dependent formation of the aggrecanase-specific aggrecan neoepitope NITEGE was visualised by immunostaining. Differences between groups were calculated using a one-way ANOVA with a Bonferroni post hoc test.ResultsAdministration of IL-10 significantly prevented the TNF-α-related cell death (P .001), release of NO (P .003) and NOS2 expression (P .04). Release of GAG fragments (P .001), NITEGE formation and expression of MMP3 (P .007), -13 (P .02) and ADAMTS4 (P .001) were significantly reduced. The TNF-α-dependent increase in COL10A1 expression was also antagonized by IL-10 (P .02).ConclusionIL-10 prevented crucial mechanisms of meniscal degeneration induced by a key cytokine of OA, TNF-α. Administration of IL-10 might improve the biological regeneration and provide a treatment approach in degenerative meniscus injuries and in conditions of post-traumatic sports injuries.
Highlights
Joint inflammation causes meniscus degeneration and can exacerbate post-traumatic meniscus injuries by extracellular matrix degradation, cellular de-differentiation and cell death
Reconcilable with the results seen for the nitric oxide (NO) release, messenger RNA (mRNA) expression of nitric oxide synthetase 2 (NOS2) was significantly reduced by addition of interleukin 10 (IL-10) (TNF-α [10 ng/ml]: 6.08 fold [4.09–8.09], P < 0.001; Tumor necrosis factor alpha (TNF-α) [100 ng/ml]: 9.78 fold [2.69–16.9; P = 0.004])
Taken together we can conclude that IL-10 has potential to reduce oxidative stress under inflammatory conditions in meniscus tissue and that this is in part mediated by inhibition of NOS2 transcription
Summary
Joint inflammation causes meniscus degeneration and can exacerbate post-traumatic meniscus injuries by extracellular matrix degradation, cellular de-differentiation and cell death. Meniscus degeneration takes place as a biomechanical adaptation to elevated loads and is accompanied by fibrocartilage formation and calcification in the medial meniscus posterior horn, which in turn is associated with the degree of the tear [6]. Both mechanisms are known to impair the resistance to tension and act as adaptation to increased mechanical overload [7, 8]. The intrinsic repair capacity of the meniscus tissue is significantly inhibited at high concentrations of TNF-α (10 ng/ml) [18]
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