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Previous studies indicate an implication of the terminal complement complex (TCC) in disc degeneration (DD). To investigate the functional role of TCC in trauma-induced DD in vivo, the model of endplate (EP) drilling was first applied in rabbits using a C6-deficient rabbit strain in which no TCC formation was possible. In parallel the model of needle puncture was investigated. Using a minimally invasive surgical intervention, lumbar rabbit intervertebral discs (IVDs) were treated with EP drilling or needle puncture. Degenerative effects of both surgical interventions were assessed by Pfirrmann grading and T2 quantification of the IVDs based on high-resolution MRI (11.7 T), as well as radiographic determination of disc height index. Pfirrmann grading indicated significant degenerative effects after EP drilling. Contrary to our assumption, no evidence was found that the absence of TCC formation in C6-deficient rabbits reduces the development of DD compared to C6-sufficient animals. EP drilling was proven to be suitable for application in rabbits. However, results of the present study do not provide clear evidence of a central functional role of TCC within DD and suggest that TCC deposition in DD patients may be primarily considered as a marker of complement activation during DD progression. [ABSTRACT FROM AUTHOR]

Accumulation of dysfunctional chondrocytes has detrimental consequences on the cartilagehomeostasis and is thus thought to play a crucial role during the pathogenesis of osteoarthritis(OA). However, the underlying mechanisms of phenotypical alteration in chondrocytes areincompletely understood. Here, we provide evidence that disruption of the intracellularvimentin network and consequent phenotypical alteration in human chondrocytes results in anexternalization of the intermediate filament. The presence of the so-called cell surfacevimentin (CSV) on chondrocytes was associated with the severity of tissue degeneration inclinical OA samples and was enhanced after mechanical injury of cartilage tissue. By meansof a doxorubicine-based in vitro model of stress-induced premature senescence (SIPS), wecould confirm the connection between cellular senescence and amount of CSV. AlthoughsiRNA-mediated silencing of CDKN2A clearly reduced the senescent phenotype as well asCSV levels of human chondrocytes, cellular senescence could not be completely reversed. Interestingly, knockdown of vimentin resulted in a SIPS-like phenotype and consequentlyincreased CSV. Therefore, we concluded that the integrity of the intracellular vimentinnetwork is crucial to maintain cellular function in chondrocytes. This assumption could beconfirmed by chemically-induced collapse of the vimentin network, which resulted in cellularstress and enhanced CSV expression. Regarding its biological function, CSV was found to beassociated with enhanced chondrocyte adhesion and plasticity. While osteogenic capacitiesseemed to be enhanced in chondrocytes expressing high levels of CSV, the chondrogenicpotential was clearly compromised. Overall, our study reinforces the importance of thevimentin network in maintenance of the chondrogenic phenotype and introduces CSV as anovel membrane-bound marker of dysfunctional chondrocytes. [ABSTRACT FROM AUTHOR]

(1) In order to enable a more widespread use of uncemented titanium-based endoprostheses to replace cobalt-containing cemented endoprostheses for joint replacement, it is essential to achieve optimal osseointegrative properties and develop economic fabrication processes while retaining the highest biomedical quality of titanium materials. One approach is the usage of an optimized form of Ti6Al4V-precision casting for manufacturing. Besides the chemical and physical properties, it is necessary to investigate possible biological influences in order to test whether the new manufacturing process is equivalent to conventional methods. (2) Methods: Primary human osteoblasts were seeded on discs, which were produced by a novel Ti6Al4V centrifugal-casting process in comparison with standard machined discs of the same titanium alloy. In a second step, the surfaces were modified by calcium or phosphorus ion beam implantation. In vitro, we analyzed the effects on proliferation, differentiation, and apoptotic processes. (3) Results: SEM analysis of cells seeded on the surfaces showed no obvious differences between the reference material and the cast material with or without ion implantation. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferation assay also did not reveal any significant differences. Additionally, the osteogenic differentiation process tested by quantitative polymerase chain reactions (PCR), Alizarin red S assay, and C-terminal collagen type I propeptide (CICP) Elisa was not significantly modified. No signs of induced apoptosis were observed. (4) Conclusions: In this study, we could show that the newly developed process of centrifugal casting generated a material with comparable surface features to standard machined Ti6Al4V material. In terms of biological impact on primary human osteoblasts, no significant differences were recognized. Additional Ca- or P-ion implantation did not improve or impair these characteristics in the dosages applied. These findings indicate that spin casting of Ti6Al4V may represent an interesting alternative to the production of geometrically complex orthopedic implants.

Objective: To investigate whether osteoarthritis (OA)‐specific assessment values (i.e., Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) and generic pain and function (visual analog scale, Hanover Functionality Status Questionnaire) measured before and 12 months after arthroplasty are associated with the risk of long‐term mortality in a cohort of patients with advanced OA of the hip or knee. Methods: The Ulm Osteoarthritis Study was a prospective cohort study of OA patients with unilateral total hip or knee replacement between January 1995 and December 1996. Correlation coefficients were calculated to describe the agreement between the different assessments. Mortality was assessed during the follow‐up period (last update July 2019). Cox proportional regression models were used to estimate hazard ratios (HRs) for mortality after adjusting for covariates. Results: Arthroplasty was accompanied by a clear reduction in pain and improved function throughout all assessments in the 706 included patients. The results of the adjusted Cox models showed no relationship between baseline and follow‐up joint‐specific WOMAC assessments and long‐term mortality. However, an independent increased risk of mortality was found with generic function assessments. In the final adjusted model, the HR for the 12‐month follow‐up value was 1.79 (95% confidence interval 1.24–2.60) in the group with clinically relevant impairment versus the reference group. Conclusion: Poor function based on the generic assessment was associated with increased long‐term mortality, suggesting that functional impairments in daily life activities may be more important for long‐term survival than OA‐specific impairments in this patient group. [ABSTRACT FROM AUTHOR]