Sodium butyrate protects against oxidative stress in human nucleus pulposus cells via elevating PPARγ-regulated Klotho expression.

We investigated the involvement of klotho in the inhibition of oxidative stress by sodium butyrate (NaB) in human nucleus pulposus cells (NPCs). NPCs were pretreated with different concentrations of NaB for 2 h before stimulation with tert-butyl hydroperoxide (TBHP). NaB alleviated TBHP-induced oxidative injury in the NPCs, as evident by the reduced accumulation of mitochondrial superoxide, intracellular reactive oxygen species, and malondialdehyde, and increased activities of superoxide dismutase and glutathione peroxidase. Flow cytometry and western blotting showed that TBHP-induced apoptosis of NPCs was inhibited by NaB. NaB also reduced the TBHP-induced release of proteases that degrade the extracellular matrix, including matrix metalloproteinases 3 and 13, and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs 4). Intriguingly, NaB significantly reversed TBHP-induced klotho suppression. However, the protective effects of NaB on NPCs were abolished by klotho-specific small interfering RNA (siRNA). TBHP stimulation had no obvious effects on total or nuclear expression of peroxisome proliferator-activated receptor γ (PPARγ), but significantly reduced PPARγ acetylation and transcriptional activity, which were restored by NaB. TBHP stimulation also promoted the nuclear translocation of histone deacetylase 3 (HDAC3) and enhanced the association between HDAC3 and PPARγ in the nucleus, but this interaction was substantially disrupted by NaB. siRNA-induced HDAC3 knockdown significantly increased PPARγ acetylation and transactivation, reversing the TBHP-induced suppression of klotho. Therefore, NaB alleviates TBHP-induced oxidative stress in human NPCs by elevating PPARγ-regulated klotho expression. HDAC3 may be a critical HDAC subtype that mediates the regulation of PPARγ activity by NaB under oxidative stress.

A Randomized Controlled Trial on the Effects of Low-Dose Extracorporeal Shockwave Therapy in Patients With Knee Osteoarthritis.

OBJECTIVE: To test the efficacy of low-dose extracorporeal shockwave therapy (ESWT) on osteoarthritis knee pain, lower limb function, and cartilage alteration for patients with knee osteoarthritis. DESIGN: Randomized controlled trial with placebo control. SETTING: Outpatient physical therapy clinics within a hospital network. PARTICIPANTS: Eligible volunteers (N=63) with knee osteoarthritis (Kellgren-Lawrence grade II or III) were randomly assigned to 2 groups. INTERVENTIONS: Patients in the experimental group received low-dose ESWT for 4 weeks while those in the placebo group got sham shockwave therapy. Both groups maintained a usual level of home exercise. MAIN OUTCOME MEASURES: Knee pain and physical function were measured using a visual analog scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lequesne index at baseline, 5 weeks, and 12 weeks. Cartilage alteration was measured analyzing the transverse relaxation time (T2) mapping. RESULTS: The VAS score, WOMAC, and Lequesne index of the ESWT group were significantly better than those of the placebo group at 5 and 12 weeks (P<.05). Both groups showed improvement in pain and disability scores over the 12-week follow-up period (P<.05). In terms of imaging results, there was no significant difference in T2 values between groups during the trial, although T2 values of the ESWT group at 12 weeks significantly increased compared to those at baseline (P=.004). The number and prevalence of adverse effects were similar between the 2 groups, and no serious side effects were found. CONCLUSIONS: A 4-week treatment of low-dose ESWT was superior to placebo for pain easement and functional improvement in patients with mild to moderate knee osteoarthritis but had some negative effects on articular cartilage.