Inhibiting osteoclasts and osteoclast precursors to reduce bone resorption is an important strategy to treat osteoclast-related diseases, such as osteoporosis, inflammatory bone loss, and malignant bone metastasis. However, the mechanism by which apoptosis is induced in the osteoclasts and their precursors are not completely understood. Here, we used nitrogen-containing bisphosphonate zoledronic acid (ZA) to induce cell apoptosis in human and murine osteoclast precursors and mature osteoclast-like cells. Caspase-3-mediated cell apoptosis occurred following the ZA (100 μM) treatment. Reactive oxygen species (ROS) were also generated in a time-dependent manner. Following knock-down of the p47^phoxexpression, which is required for ROS activation, or co-treatment with the ROS inhibitor, N-acetyl-L-cysteine, ZA-induced apoptosis was significantly suppressed in both osteoclast precursors and mature osteoclast-like cells. The ROS-activated mitogen-activated protein kinases pathways did not trigger cell apoptosis. However, a ROS-regulated Mcl-1 decrease simultaneously with glycogen synthase kinase (GSK)-3β promoted cell apoptosis. These findings show that ZA induces apoptosis in osteoclast precursors and mature osteoclast-like cells by triggering ROS- and GSK-3β-mediated Mcl-1 down-regulation.

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.

Purpose: The purpose of the current study was to evaluate the effectiveness of ultrasound-guided percutaneous carpal tunnel release in hemodialysis patients with carpal tunnel syndrome. Methods: From February 2009 to April 2013, a prospective review of 113 consecutive cases of ultrasound-guided percutaneous carpal tunnel release was carried out in 84 hemodialysis patients. Results were analyzed by clinical subjective scale, two self-administered questionnaires, and functional evaluations at seven time points (1 week and 1, 3, 6, 12, 18, and 24 months). Results: Satisfactory symptom improvement in patients was 82%, 80%, 86%, 89%, 90%, 91%, and 90% at 1 week and 1, 3, 6, 12, 18, and 24 months postoperatively, respectively. Moderate pain was suffered in 11.5% of patients within 1 week, 8.8% within 1 month, 2.7% within 3 months, and none after 12 months postoperatively. Static two-point discrimination and Semmes–Weinstein monofilament examinations presented significant improvements after 1 week and 1 month postoperatively and with time. Postoperative grip power demonstrated recovery and a significant increase after 3 and 6 months postoperatively. Three-jaw chuck-pinch strength showed significant increase after 1 month postoperatively. There were no operative complications. Conclusion: Ultrasound-guided percutaneous carpal tunnel release is an effective and safe procedure in hemodialysis patients with carpal tunnel syndrome. The advantages include a less invasive procedure, no tourniquet needed, only limited infiltration anesthesia, minimal soft-tissue exploration, and relatively short operation time. Our data suggest this technique can reliably relieve clinical symptoms, with early restoration of grip and pinch strength.