IL-1ß induces changes in expression of core circadian clock components PER2 and BMAL1 in primary human chondrocytes through the NMDA receptor/CREB and NF-κB signalling pathways.

The circadian clock is a specialised cell signalling circuit present in almost all cells. It controls the timing of key cell activities such as proliferation and differentiation. In osteoarthritis, expression of two components of the circadian clock, BMAL1 and PER2 is altered in chondrocytes and this change has been causally linked with the increase in proliferation and altered chondrocyte differentiation in disease. IL-1ß, an inflammatory cytokine abundant in OA joints, has previously been shown to induce changes in BMAL1 and PER2 expression in chondrocytes. The purpose of this study is to identify the mechanism involved. We found IL-1ß treatment of primary human chondrocytes led to activation of NMDA receptors as evidenced by an increase in phosphorylation of GluN1 and an increase in intracellular calcium which was blocked by the NMDAR antagonist MK801. Levels of phosphorylated CREB were also elevated in IL-1ß treated cells and this effect was blocked by co-treatment of cells with IL-1ß and the NMDAR antagonist MK-801. Knockdown of CREB or inhibition of CREB activity prevented the IL-1ß induced increase in PER2 expression in chondrocytes but had no effect on BMAL1. Phosphorylated p65 levels were elevated in IL-1ß treated chondrocytes indicating increased NF-κB activation. Inhibition of NF-κB activity prevented the IL-1ß induced reduction in BMAL1 expression and partially mitigated the IL-1ß induced increase in PER2 expression in chondrocytes. These data indicate that the NMDAR/CREB and NF-κB signalling pathways regulate the core circadian clock components PER2 and BMAL1 in chondrocytes. Given that changes in expression of these clock components have been observed in a wide range of diseases, these findings may be broadly relevant for understanding the mechanism leading to circadian clock changes in pathology.

Risk analysis of patients with an osteolytic acetabular defect after total hip arthroplasty using subject-specific finite-element modelling.

AIMS: Osteolysis, secondary to local and systemic physiological effects, is a major challenge in total hip arthroplasty (THA). While osteolytic defects are commonly observed in long-term follow-up, how such lesions alter the distribution of stress is unclear. The aim of this study was to quantitatively describe the biomechanical implication of such lesions by performing subject-specific finite-element (FE) analysis on patients with osteolysis after THA. PATIENTS AND METHODS: A total of 22 hemipelvis FE models were constructed in order to assess the transfer of load in 11 patients with osteolysis around the acetabular component of a THA during slow walking and a fall onto the side. There were nine men and two women. Their mean age was 69 years (55 to 81) at final follow-up. Changes in peak stress values and loads to fracture in the presence of the osteolytic defects were measured. RESULTS: The von Mises stresses were increased in models of those with and those without defects for both loading scenarios. Although some regions showed increases in stress values of up to 100%, there was only a moderate 11.2% increase in von Mises stress in the series as a whole. The site of fracture changed in some models with lowering of the load to fracture by 500 N. The most common site of fracture was the pubic ramus. This was more frequent in models with larger defects. CONCLUSION: We conclude that cancellous defects cause increases in stress within cortical structures. However, these are likely to lead to a modest decrease in the load to fracture if the defect is large (> 20cm3) or if the patient is small with thin cortical structures and low bone mineral density. Cite this article: Bone Joint J 2018;100-B:1455-62.

The use of a lipped acetabular liner decreases the rate of revision for instability after total hip replacement: a study using data from the New Zealand Joint Registry.

We compared the rate of revision for instability after total hip replacement (THR) when lipped and non-lipped acetabular liners were used. We hypothesised that the use of a lipped liner in a modular uncemented acetabular component reduces the risk of revision for instability after primary THR. Using data from the New Zealand Joint Registry, we found that the use of a lipped liner was associated with a significantly decreased rate of revision for instability and for all other indications. Adjusting for the size of the femoral head, the surgical approach and the age and gender of the patient, this difference remained strongly significant (p < 0.001). We conclude that evidence from the New Zealand registry suggests that the use of lipped liners with modular uncemented acetabular components is associated with a decreased rate of revision for instability after primary THR.

Tapered fluted modular titanium stems in the management of Vancouver B2 and B3 peri-prosthetic fractures.

Tapered, fluted, modular, titanium stems are increasingly popular in the operative management of Vancouver B2 and selected B3 peri-prosthetic femoral fractures. We have reviewed the results at our institution looking at stem survival and clinical outcomes and compared this with reported outcomes in the literature. Stem survival at a mean of 54 months was 96% in our series and 97% for combined published cases. Review of radiology showed maintenance or improvement of bone stock in 89% of cases with high rates of femoral union. Favourable clinical outcome scores have reported by several authors. No difference in survival or clinical scores was observed between B2 and B3 fractures. Tapered stems are a useful option in revision for femoral fracture across the spectrum of femoral bone deficiency.

Role and results of tapered fluted modular titanium stems in revision total hip arthroplasty.

Tapered, fluted, modular, titanium stems have a long history in Europe and are increasing in popularity in North America. We have reviewed the results at our institution looking at stem survival and clinical outcomes. Radiological outcomes and quality of life assessments have been performed and compared to cylindrical non-modular cobalt chromium stems. Survival at five years was 94%. This fell to 85% at ten years due to stem breakage with older designs. Review of radiology showed maintenance or improvement of bone stock in 87% of cases. Outcome scores were superior in tapered stems despite worse pre-operative femoral deficiency. Tapered stems have proved to be a useful alternative in revision total hip arthroplasty across the spectrum of femoral bone deficiency.

Articulating antibiotic impregnated spacers in two-stage revision of infected total knee arthroplasty.

Antibiotic impregnated articulating spacers are used in two-stage revision total knee arthroplasty to deliver local antibiotic therapy while preserving function. We have observed infection control in greater than 95% of cases with functional outcomes approaching those seen in revision for aseptic loosening. Higher failure has been observed with methicillin resistant organisms.