The upregulation of tumor necrosis factor-alpha (TNF-α) is a common event in arthritis, and the subsequent signaling cascade that leads to tissue damage has become the research focus. To explore a potential therapeutic strategy to prevent cartilage degradation, we tested the effect of ginsenoside Rg3, a bioactive component of Panax ginseng, on TNF-α-stimulated chondrocytes.TC28a2 Human Chondrocytes were treated with TNF-α to induce damage of chondrocytes. SIRT1 and PGC-1a expression levels were investigated by Western blotting assay. Mitochondrial SIRT3 and acetylated Cyclophilin D (CypD) were investigated using mitochondrial isolation. The mitochondrial mass number and mitochondrial DNA copy were studied for mitochondrial biogenesis. MitoSOX and JC-1 were used for the investigation of mitochondrial ROS and membrane potential. Apoptotic markers, pro-inflammatory events were also tested to prove the protective effects of Rg3. We showed Rg3 reversed the TNF-α-inhibited SIRT1 expression. Moreover, the activation of the SIRT1/PGC-1α/SIRT3 pathway by Rg3 suppressed the TNF-α-induced acetylation of CypD, resulting in less mitochondrial dysfunction and accumulation of reactive oxygen species (ROS). Additionally, we demonstrated that the reduction of ROS ameliorated the TNF-α-elicited apoptosis. Furthermore, the Rg3-reverted SIRT1/PGC-1α/SIRT3 activation mediated the repression of p38 MAPK, which downregulated the NF-κB translocation in the TNF-α-treated cells. Our results revealed that administration of Rg3 diminished the production of interleukin 8 (IL-8) and matrix metallopeptidase 9 (MMP-9) in chondrocytes via SIRT1/PGC-1α/SIRT3/p38 MAPK/NF-κB signaling in response to TNF-α stimulation. Taken together, we showed that Rg3 may serve as an adjunct therapy for patients with arthritis.

Background: The treatment of complex persistent elbow instability after trauma is challenging. Previous studies on treatments have reported varied surgical techniques, which makes it difficult to establish a therapeutic algorithm. Furthermore, the surgical procedures may not sufficiently restore elbow stability, even with an additional device, and a noted high rate of arthritis progression.While a recently developed internal joint stabilizer effectively treats elbow instability, its clinical application for complex persistent elbow instability is limited and the standardized protocol is not well described. Additionally, we want to know whether the arthritis progression will cause a negative impact on the functional outcomes of complex persistent elbow instability. Questions/purposes: (1) Does treatment of complex persistent elbow instability with a hinged internal joint stabilizer and a standardized protocol prevent recurrent instability and other complications? (2) What are the pre- to postoperative improvements in pain, disability, elbow performance, and ROM? (3) Is the development of post-traumatic arthritis associated with worse pain, disability, elbow performance, and ROM? Methods: Between September 2014 and October 2019, we treated 22 patients for persistent dislocation or subluxation after initial treatment of traumatic elbow fracture-dislocations. Of those, we considered patients who were at least 20 years of age, with an interval of 6 weeks or more between the injury (initial treatment) and the index reconstructive procedure, which had been performed at our institute, as potentially eligible. During that time, we used an internal joint stabilizer with a standardized protocol for posttraumatic complex persistent elbow instability. We performed total elbow replacements in patients older than 50 years who had advanced elbow arthritis. Based on that, 82% (18 of 22) of patients were eligible; 14% (3 of 22) were excluded because total elbow replacements was undertaken, and another 5% (1 of 22) were lost before the minimum study follow-up of 1 year (median 24 months [range 12 to 63]), leaving 64% (14 of 22) for analysis in this retrospective study. We treated 14 patients (14 elbows) with posttraumatic complex persistent elbow instability with an internal joint stabilizer and a standardized protocol that comprised debridement arthroplasty with ulnar neurolysis, restoration of bony and ligamentous (reattachment) structures, application of an internal joint stabilizer, and early rehabilitation. There were eight men and six women in this study, with a median (range) age of 44 years (21 to 68). The initial elbow fracture-dislocation injury pattern was a terrible triad injury in seven patients, a posterolateral rotatory injury in four patients, and a posterior Monteggia fracture in three patients. Preoperative and follow-up radiographs were reviewed for evidence of recurrent instability and arthritis. Complications such as wound infection, seroma, neurovascular injury, and hardware complications were ascertained through chart review. Preoperative and postoperative VAS score for pain, DASH, and Mayo Elbow Performance Scores (MEPS) were collected and compared. Furthermore, extension-flexion and supination-pronation arcs were collected by chart review. We divided the patients into two groups according to whether or not they developed posttraumatic arthritis. We then presented the differences between pain, disability, elbow performance, and ROM. The hinged internal joint stabilizer was removed using another open procedure under general anesthesia 6 to 8 weeks after surgery. Results: There were no recurrent instability during and after device removal. Seven patients developed complications, including wound infection, seroma, neurovascular injury, hardware complications, and heterotopic ossification. Two patients had complications related to internal joint stabilizers and three had complications linked to radial head prostheses. Median (range) preoperative to postoperative changes included decreased pain (VAS 5 [2 to 9] to 0 [0 to 3], difference of medians -5; p < 0.001), decreased disability (DASH 41 [16 to 66] to 7 [0 to 46], difference of medians -34; p < 0.001), improved function (MEPS 60 [25 to 70] to 95 [65 to 100], difference of medians 35; p < 0.001), improved extension-flexion arc (40° [10° to 70°] to 113° [75° to 140°], difference of medians 73°; p < 0.001), and supination-pronation arc (78° [30° to 165°] to 148° [70° to 175°], difference of medians 70°; p < 0.001). Between patients with and without development of post-traumatic arthritis, there were no differences in postoperative pain (VAS 0 [0 to 3] to 0 [0 to 1], difference of medians 0; p = 0.17), disability (DASH 7 [0 to 46] to 7 [0 to 18], difference of medians 0; p = 0.40), function (MEPS 80 [65 to 100] to 95 [75 to 100], difference of medians 15; p = 0.79), extension-flexion arc (105° [75° to 140°] to 115° [80° to 125°], difference of medians 10°; p = 0.40), and supination-pronation arc (155° [125° to 175°] to 135° [70° to 160°], difference of medians -20°; p < 0.18). Conclusion: In this small, retrospective study, we found that an internal joint stabilizer with a standardized treatment protocol could maintain concentric reduction while allowing early functional motion, and that it could improve clinical outcomes for patients with complex persistent elbow instability. However, patients must be counseled that the complications related to the radial head prostheses may occur, and that the benefits of early motion must compensate for an additional removal procedure and the risk of seroma formation. Level of Evidence: Level IV, therapeutic study.

Cisplatin is a potent and efficacious anticancer medication. In pediatric cancer, the height of the growth plate’s proliferating layer is known to be reduced by cisplatin, but researchers have not yet determined the specific mechanism behind this phenomenon. Lectin-like oxidized low-density lipoprotein receptor-1 is known to be involved in the development of osteoarthritis and atherosclerosis. The equilibrium of cartilage is regulated by LOX-1, but the function of LOX-1 in cisplatin-induced chondrocyte impairment remains unknown. Positive regulation of LOX-1 leads to increased cellular oxidative stress and cell damage. Research has shown that blocking of LOX-1 can reduce the chondrocyte damage and oxidative stress in cells induced by oxidized LDL treatment. However, the role of LOX-1 in cisplatin-mediated chondrocyte damage is still unclear. This study found that cisplatin increased ROS concentration and p38, ERK phosphorylation. Cisplatin activated NF-κB in chondrocytes. In addition, LOX-1 small interfering RNA transfection mitigated cisplatin-induced apoptosis in TC28a2 cells. Phosphorylated extracellular signal-regulated kinase and p38 were dose-dependently increased by administration of cisplatin. Silencing LOX-1 or MAPK inhibition reduces cisplatin-caused apoptosis. The findings suggest that cisplatin-induced growth plate dysfunction operates through the LOX-1/p38/NF-κB signaling pathway.