Single impact cartilage trauma and TNF-α: Interactive effects do not increase early cell death and indicate the need for bi-/multidirectional therapeutic approaches

Abstract

Blunt trauma of articular cartilage, often resulting from accidents or sports injuries, is associated with local inflammatory reactions and represents a major risk factor for development of post-traumatic osteoarthritis. TNF-α is increased in synovial fluid early after trauma, potentiates injury-induced proteoglycan degradation and may act proapoptotic under permissive conditions. We asked whether TNF-α also influences chondrocyte death, gene expression of catabolic and anabolic markers and the release of proinflammatory mediators in the early post-traumatic phase. Interactive effects of a defined single impact trauma (0.59 J) and TNF-α (100 ng/ml) on human early-stage osteoarthritic cartilage were investigated in vitro over 24 h. Exposure of traumatized cartilage to TNF-α did not increase chondrocyte death. IL-6-synthesis was augmented by trauma, TNF-α and combined treatment. The impact increased the release of PGE2 and PGD2 in the presence and absence of TNF-α to a similar extent while TNF-α alone showed no effect. In contrast, NOS2A-expression and nitric oxide (NO)-release were not affected by trauma but significantly increased by TNF-α. Expression of OPG and RANKL was not affected by TNF-α but modulated by trauma. TNF-α with and without trauma significantly induced MMP1 gene expression. These results indicate that TNF-α does not potentiate early cell death in early-stage osteoarthritic cartilage after blunt injury. However, trauma and TNF-α showed independent and interactive effects concerning prostaglandin and NO release. TNF-α probably contributes to cartilage degradation after trauma by an early induction of MMP1 gene expression. Our study confirms that an anti-TNF-α therapy may have inhibitory effects on catabolic and, partly, on inflammatory processes after a single impact trauma. As TNF-α does not contribute to the loss of chondrocytes in the initial post-traumatic phase, a combination with pharmaco-therapeutic strategies reducing early cell death could be reasonable.

Differential Interactive Effects of Cartilage Traumatization and Blood Exposure In Vitro and In Vivo

“…The significant reduction in cell viability after cartilage impact corresponds to our previous findings. 14,20 The effect of blood supports other studies measuring increased lactate dehydrogenase release and chondrocyte apoptosis in a coculture of human cartilage and whole blood. 16 For the first time, a significant, additive effect of combined cartilage trauma and blood exposure on cell viability after 4 days could be shown, indicating that, in vitro, a singular blood exposure strongly aggravates trauma-induced cell death in cartilage.…”

“…It is possible that osteoarthritic chondrocytes are more susceptible to cell death under culture conditions due to apoptotic processes induced by OA. 1 Nevertheless, we could show typical trauma effects in the described tissue culture model, 14,20 indicating a typical reaction of the cartilage to mechanical impact. Furthermore, Jansen et al 18 reported an equal vulnerability of healthy and degenerated cartilage to blood-induced damage.…”

“…However, IL-1b and TNFa did not aggravate cell loss in impacted cartilage. 14,20 Another possible incident in joint injuries is the occurrence of a trauma-induced hemarthrosis. Several in vitro studies have revealed a cartilage-damaging effect of blood or specific blood cells, including the reduction of chondrocyte viability.…”

Role of miR-146a in human chondrocyte apoptosis in response to mechanical pressure injury in vitro

“…The delayed, secondary injury is considered to be due to a cascade of biochemical reactions that are important in the mechanisms of OA. As cellular and micron-sized structural changes in vivo are hard to detect immediately post-injury, research on joint mechanical injury has focused on understanding the mechanisms of the secondary step that accounts for chondrocytes damaged by mechanical injury in vitro (6–8). …”

Characterization of a migrative subpopulation of adult human nasoseptal chondrocytes with progenitor cell features and their potential for in vivo cartilage regeneration strategies

“…For quantitative real-time PCR-analysis of ALPL, the TaqMan ® Gene Expression Assay Hs01029144_m1 was used with TaqMan ® Gene Expression Master Mix in a StepOnePlusTM Real-Time PCR System (all from Applied Biosystems, Darmstadt, Germany). The ALPL expression level was normalized to 18S rRNA as described [ 58 ].…”