IL-10 ameliorates TNF-α induced meniscus degeneration in mature meniscal tissue in vitro

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.

Single-cell RNA-seq analysis identifies meniscus progenitors and reveals the progression of meniscus degeneration

“…Iwata et al revealed that CD318 is a CD146 negative subset of bone marrow fibroblasts and regulates cytokine expression 44. Previous studies have shown that inflammatory cytokines such as IL-1β and TNF-α induce meniscus metabolic responses and result in degeneration 28 45. In our study, IL-1β was used to induce the inflammatory response in human meniscus cells.…”

Substantive molecular and histological changes within the meniscus with tears

“…The roles of matrix metalloproteinases 13 (MMP13) and an 'aggrecanase' known as a disintegrin and metalloproteinase with thrombospondin motifs − 5 (ADAMTS5), in OA through the degradation of ECM are well established [12][13][14]. It is also clear that type X collagen (COL10A1) is a marker of fibrochondrocyte hypertrophy in meniscus [9,15], and CEBPβ contributes to the pathophysiological process of OA [16,17]. These genes whose expression level corretated with the extent of cartilage degeneration might be considered as markers of articular deterioration.…”

Circulating IL-10 is compromised in patients predisposed to developing and in patients with severe knee osteoarthritis

“…Lower circulating IL-10 corresponds with higher joint effusion of TNF-α, localized and systemic indices of cartilage degeneration, and greater histological evidence of joint osteoarthritis following anterior cruciate ligament transection in experimental rabbits 40 . In humans, a lower serum IL-10 is arguably mirrored by a decrease in synovial fluid IL-10 12 , 41 , which in turn, could compromise joint integrity by exacerbating blood-induced cartilage damage 42 , and as demonstrated in vitro, minimize the protection against pro-inflammatory cytokine induced damage 22 – 25 . Therefore, in the absence of a robust TNF-α alteration, it is plausible that a lower serum IL-10 concentration following an anterior cruciate ligament injury could be detrimental to the joint structure by compromising the anti-inflammatory protection against pro-inflammatory cytokine-mediated cartilage loss and consequentially increase the risk of developing knee osteoarthritis.…”

“…The localized presence of TNF-α could increase the risk of osteophyte progression, joint space narrowing 19 , cartilage degradation 20 , and lower IL-10 expression 21 . IL-10 decreases TNF-α production and TNF-α mediated events associated with osteoarthritis development 22 – 25 , thereby suggesting the pathophysiological importance of a regulated anti- and pro-inflammatory cytokine balance on joint integrity. Although an increased production of IL-10 and TNF-α from whole blood associates with the progression in knee osteoarthritis 26 , and preliminary results indicate that local and circulating cytokine concentrations decrease with severe compared to moderate knee osteoarthritis 27 , 28 , it is unknown if the circulating pro- to anti-inflammatory cytokine balance (i.e., ratio) is altered with the radiographic severity in knee osteoarthritis.…”