Nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is key in maintaining redox homeostasis and the pathogenesis of osteoarthritis (OA) involves oxidative distress. We thus investigated whether Nrf2/ARE signaling may control expression of key chondrogenic differentiation and hyaline cartilage maintenance factor SOX9.

In human C-28/I2 chondrocytes SOX9 expression was measured by RT–qPCR after shRNA-mediated knockdown of Nrf2 or its antagonist the Kelch-like erythroid cell-derived protein with cap “n” collar homology-associated protein 1 (Keap1). Putative ARE-binding sites in the proximal SOX9 promoter region were inactivated, cloned into pGL3, and co-transfected with phRL–TK for dual-luciferase assays to verify whether Nrf2 transcriptionally regulates SOX9. SOX9 promoter activity without and with Nrf2-inducer methysticin were analyzed. Sox9 expression in articular chondrocytes was correlated to cartilage thickness and degeneration in wild-type (WT) and Nrf2-knockout mice. Data were analyzed by one-way ANOVA, a Student's t-test, or Wilcoxon rank-sum test, according to the normal distribution. Statistical significance was set to p < 0.05.

While Keap1-specific RNAi increased SOX9 expression, Nrf2-specific RNAi significantly decreased it. Putative ARE sites (ARE₁, ARE₂) were identified in the SOX9 promoter region. ARE₂ mutagenesis significantly reduced SOX9 promoter activity, while truncation of ARE₁ did not. A functional ARE₂ site was thus essential for methysticin-mediated induction of SOX9 promoter activity. Knee cartilage of young Nrf2-knockout mice further revealed significantly fewer Sox9-positive chondrocytes as compared to old Nrf2-knockout animals, which further showed thinner cartilage and more severe cartilage erosion.

Our data suggest that SOX9 expression in articular cartilage is directly Nrf2-dependent and that pharmacological Nrf2 activation may hold potential to diminish age-dependent osteoarthritic changes in knee cartilage through improving protective SOX9 expression.

Helical plates potentially bypass the medial neurovascular structures of the thigh. Recently, two plate designs (90°- and 180°-helix) proved similar biomechanically behaviour compared to straight plates. Aims of this study were: (1) Feasibility of MIPO-technique with 90°- and 180°-helical plates on the femur, (2) Assessment of distances to adjacent anatomical structures at risk, (3) Comparison of these distances to using medial straight plates instead, (4) Correlation of measurements performed in anatomic dissection with CT-angiography.

MIPO was performed in ten cadaveric femoral pairs using either a 90°-helical 14-hole-LCP (Group1) or a 180°-helical 15-hole-LCP-DF (Group2). CT angiography was used to evaluate the distances between the plates and the femoral arteries as well as the distances between the plates and the perforators. Subsequently, the specimens were dissected, and the distances were determined again manually. Finally, all helical plates were removed, and all measurements were repeated after application of straight medial plates (Group3).

Closest overall distances between plates and femoral arteries were 15 mm (11 − 19 mm) in Group1, 22 mm (15 − 24 mm) in Group2 and 6 mm (1 − 8 mm) in Group3 with a significant difference between Group1 and Group3 (p < 0.001). Distances to the nearest perforators were 24 mm (15 − 32 mm) in Group1 and 2 mm (1 − 4 mm) in Group2. Measurement techniques (visual after surgery and CT-angiography) demonstrated a strong correlation of r² = 0.972 (p < 0.01).

MIPO with 90°- and 180°-helical plates is feasible and safe. Attention must be paid to the medial neurovascular structures with 90°-helical implants and to the proximal perforators with 180°-helical implants. Helical implants can avoid medial neurovascular structures compared to straight plates although care must be taken during their distal insertion. Measurements during anatomical dissection correlate with CT-angiography.

Proximal humeral shaft fractures are commonly treated with long straight locking plates endangering the radial nerve distally. The aim of this study was to investigate the biomechanical competence in a human cadaveric bone model of 90°-helical PHILOS plates versus conventional straight PHILOS plates in proximal third comminuted humeral shaft fractures.

Eight pairs of humeral cadaveric humeri were instrumented using either a long 90°-helical plate (group1) or a straight long PHILOS plate (group2). An unstable proximal humeral shaft fracture was simulated by means of an osteotomy maintaining a gap of 5cm. All specimens were tested under quasi-static loading in axial compression, internal and external rotation as well as bending in 4 directions. Subsequently, progressively increasing internal rotational loading until failure was applied and interfragmentary movements were monitored by means of optical motion tracking.

Flexion/extension deformation (°) in group1 was (2.00±1.77) and (0.88±1.12) in group2, p=0.003. Varus/valgus deformation (°) was (6.14±1.58) in group1 and (6.16±0.73) in group2, p=0.976. Shear (mm) and displacement (°) under torsional load were (1.40±0.63 and 8.96±0.46) in group1 and (1.12±0.61 and 9.02±0.48) in group2, p≥0.390. However, during cyclic testing shear and torsional displacements and torsion were both significantly higher in group 1, p≤0.038. Cycles to catastrophic failure were (9960±1967) in group1 and (9234±1566) in group2, p=0.24.

Although 90°-helical plating was associated with improved resistance against varus/valgus deformation, it demonstrated lower resistance to flexion/extension and internal rotation as well as higher flexion/extension, torsional and shear movements compared to straight plates. From a biomechanical perspective, 90°-helical plates performed inferior compared to straight plates and alternative helical plate designs with lower twist should be investigated in future paired cadaveric studies.