Importance of IL-6 trans-signaling and high autocrine IL-6 production in human osteoarthritic chondrocyte metabolism.

OBJECTIVE: Neutralization of Interleukin (IL)-6-signaling by antibodies is considered a promising tool for the treatment of osteoarthritis (OA). To gain further insight into this potential treatment, this study investigated the effects of IL-6-signaling and IL-6 neutralization on chondrocyte metabolism and the release of IL-6-signaling-related mediators by human chondrocytes. DESIGN: Chondrocytes were collected from 49 patients with advanced knee/hip OA or femoral neck fracture. Isolated chondrocytes were stimulated with different mediators to analyze the release of IL-6, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130). The effect of IL-6 and IL-6/sIL-6R complex as well as neutralization of IL-6-signaling on the metabolism was analyzed. RESULTS: OA chondrocytes showed high basal IL-6 production and release, which was strongly negatively correlated with the production of cartilage-matrix-proteins. Chondrocytes produced and released sIL-6R and sgp130. The IL-6/sIL-6R complex significantly increased nitric oxide, prostaglandin E2 and matrix metalloproteinase 1 production, decreased Pro-Collagen Type II and mitochondrial ATP production, and increased glycolysis in OA chondrocytes. Neutralization of IL-6-signaling by antibodies did not significantly affect the metabolism of OA chondrocytes, but blocking of glycoprotein 130 (gp130)-signaling by SC144 significantly reduced the basal IL-6 release. CONCLUSION: Although IL-6 trans-signaling induced by IL-6/sIL-6R complex negatively affects OA chondrocytes, antibodies against IL-6 or IL-6R did not affect chondrocyte metabolism. Since inhibition of gp130-signaling reduced the enhanced basal release of IL-6, interfering with gp130-signaling may ameliorate OA progression because high cellular release of IL-6 correlates with reduced production of cartilage-matrix-proteins.

Biomechanical Comparison of Cannulated Screw Osteosynthesis With Tension-Band Wiring for Proximal Fractures of the Fifth Metatarsal (Jones Fracture).

Jones fractures, which lie at the junction of the diaphysis to the metaphysis of the fifth metatarsal, are a well-described clinical issue. There are various surgical approaches, including the commonly performed cannulated screw osteosyntheses, and the less frequently used tension-band approach. The aim is to compare the biomechanical stability of these osteosyntheses. We performed an osteotomy on 16 fresh frozen fifth metatarsal bones from body donors representing a Jones fracture. The fractures were treated pairwise with screw osteosynthesis or tension-band wiring. This was followed by cyclic axial bending until osteosynthesis failure. Stability under axial bending force was higher in the screw osteosynthesis (mean: 70.0 ± 66.5 N) compared to the tension-band wiring (mean: 35.7 ± 23.3 N) group although not reaching statistical significance (p = .116). The study shows no statistically significant difference in biomechanical stability under axial loading between screw osteosynthesis and tension band wiring. Based on the data obtained, no differences can be observed from a biomechanical point of view. The study supports the established method of treating Jones fractures primarily with screw osteosynthesis. In addition, the data suggest that tension band wiring may be a good alternative osteosynthesis, for example, after failed casting treatment or failure of primary osteosynthesis.

Biomechanical Comparison of Medio-Plantar and Plantar Plate Fixation for First Tarsometatarsal Joint Arthrodesis.

Plantar plate positioning has been demonstrated as biomechanically superior. However, some operators remain resentful about the morbidity of the surgical approach. To provide improved plate fixation for first tarsometatarsal joint arthrodesis with respect to the tibialis anterior tendon, a medio-plantar plate was developed. The purpose of this biomechanical study was to compare its construct stability to that of a plantar plate construct. Twelve pairs of fresh frozen human specimens were used in a matched pair test. Each pair was fixed with a 4 mm compression screw and either a plantar locking plate or a medio-plantar locking plate. A cantilever beam test was performed in dorsiflexion. Before and after cyclic loading (5000 cycles; 40 N), bending stiffness and relative movements at the joint space were monitored in a quasi-static test including optical motion tracking. Maximum load and bending moment to failure were investigated in a load-to-failure ramp test. The bending stiffness of both groups did not significantly differ before (plantar 49.9 N/mm ± 19.2; medio-plantar 53.9 N/mm ± 25.4, p = 0.43) or after (plantar 24.4 N/mm ± 9.7; medio-plantar 35.3 N/mm ± 22.0, p = 0.08) cyclic loading but decreased significantly in both groups (p < 0.01) after cyclic loading. Relative movement increased significantly during cyclic testing in both groups (p < 0.01) but did not differ significantly between the groups before (p = 0.29) or after (p = 0.16) cyclic loading. Neither load nor bending moment to failure were significantly different (plantar 225 N ± 78, 10.8 Nm; medio-plantar 210 N ± 86, 10.1 Nm, p = 0.61). Both plate constructs provided equivalent construct stability, both being well suited for Lapidus arthrodesis.

Osteoarthritis-Induced Metabolic Alterations of Human Hip Chondrocytes.

Osteoarthritis (OA) alters chondrocyte metabolism and mitochondrial biology. We explored whether OA and non-OA chondrocytes show persistent differences in metabolism and mitochondrial function and different responsiveness to cytokines and cAMP modulators. Hip chondrocytes from patients with OA or femoral neck fracture (non-OA) were stimulated with IL-1ß, TNF, forskolin and opioid peptides. Mediators released from chondrocytes were measured, and mitochondrial functions and glycolysis were determined (Seahorse Analyzer). Unstimulated OA chondrocytes exhibited significantly higher release of IL-6, PGE2 and MMP1 and lower production of glycosaminoglycan than non-OA chondrocytes. Oxygen consumption rates (OCR) and mitochondrial ATP production were comparable in unstimulated non-OA and OA chondrocytes, although the non-mitochondrial OCR was higher in OA chondrocytes. Compared to OA chondrocytes, non-OA chondrocytes showed stronger responses to IL-1ß/TNF stimulation, consisting of a larger decrease in mitochondrial ATP production and larger increases in non-mitochondrial OCR and NO production. Enhancement of cAMP by forskolin prevented IL-1ß-induced mitochondrial dysfunction in OA chondrocytes but not in non-OA chondrocytes. Endogenous opioids, present in OA joints, influenced neither cytokine-induced mitochondrial dysfunction nor NO upregulation. Glycolysis was not different in non-OA and OA chondrocytes, independent of stimulation. OA induces persistent metabolic alterations, but the results suggest upregulation of cellular mechanisms protecting mitochondrial function in OA.

Open versus minimally invasive fixation of thoracic and lumbar spine fractures in patients with ankylosing spinal diseases.

PURPOSE: Posterior multilevel fixation of traumatic instability in ankylosing spinal disease (ASD) can be performed by open surgery (OS) or minimally invasive surgery (MIS). We investigated whether both methods differ based on the reduction results and perioperative parameters. METHODS: In this retrospective cohort study, OS and MIS groups were investigated. The bisegmental Cobb angles and dislocation angles were measured using pre- and postoperative CT images, and the initial malalignment and achieved reduction were calculated. Cut-seam time, calculated blood loss, transfusion number, fluoroscopy time, pedicle screw placement accuracy, duration of ICU stay, in-patient stay, and complications (bleeding, postoperative thrombosis and embolism, and postoperative mortality) were recorded. RESULTS: Seventy-five ASD patients with spine fractures (Ø 75 ± 11 years, male: 52, female: 23) (MIS: 48; OS: 27) were included in this study. The extent of reduction did not differ in the OS and MIS groups (p = 0.465; MIS:- 1 ± 3°, OS:-2 ± 6°). The residual postoperative malalignment angle was not significantly different (p = 0.283). Seventy-eight of the implanted screws (11%) showed malpositioning. No difference was found between OS and MIS (MIS, 37 [7%]; OS, 41 [16%]; p = 0.095). MIS was associated with less blood loss (OS: 1.28 ± 0.78 l, MIS: 0.71 ± 0.57 l, p = 0.001), cut-seam time (MIS: 98 ± 44 min, OS: 166 ± 69 min, p < 0.001), and hospital stay (MIS: Ø14 ± 16 d, OS: Ø38 ± 49 d, p = 0.02) than OS. CONCLUSION: OS and MIS show equally limited performance in terms of the fracture reduction achieved. The MIS technique was superior to OS based on the perioperative outcome. Therefore, MIS should be preferred over OS for unstable spinal injuries, excluding C-type fractures, in ASD patients without neurological impairment.