Coniferaldehyde prevents articular cartilage destruction in a murine model via Nrf2/HO­1 pathway.

Osteoarthritis (OA) is the most prevalent joint disorder characterized by progressive cartilage damage, resulting in gradual disability among the elderly. We previously provided in vivo evidence that nuclear factor erythroid 2­related factor 2 (Nrf2) deficiency is associated with the development of OA. It has been reported that coniferaldehyde (CFA) acts as a potential Nrf2 activator. The aim of the present study was to investigate the protective effects of CFA against osteoarthritis. A murine model of surgical­induced OA was used in the present study and CFA was administered by peritoneal injection every day, and the knee joints were assessed by histological analysis. The results demonstrated that CFA activated the Nrf2 signaling pathway in primary chondrocytes and articular cartilage from the knee joints. Cartilage damage in mice subjected to the destabilization of the medial meniscus was evidently alleviated by CFA treatment. CFA also robustly suppressed apoptosis induced by H2O2 in murine chondrocytes and reduced the expression of matrix metalloproteinase (MMP)1, MMP3, interleukin (IL)­1 and IL­6 in vivo. On the whole, the findings suggested that CFA exerts a therapeutic effect against OA, and the activation of the Nrf2/heme oxygenase­1 pathway may play a crucial role in CFA­mediated cartilage protection.

Ergosterol limits osteoarthritis development and progression through activation of Nrf2 signaling.

Osteoarthritis (OA) is a common joint disorder characterized by progressive articular cartilage degeneration and destruction and results in gradual disability among middle-aged and elderly patients. Our previous study demonstrated that depletion of nuclear factor erythroid 2-related factor 2 (Nrf2) exacerbated cartilage erosion in an OA model and that activation of the Nrf2 pathway could counter this process. As a downstream target of Nrf2, heme oxygenase (HO) degrades heme to free iron, biliverdin and carbon monoxide (CO), which protects against oxidative stress. Ergosterol (ER), which is extracted from fungi, is a newly discovered Nrf2 activator and displayed efficacy against myocardial injury. The present study aimed to investigate the potential protective effects of ER against cartilage damage during OA. Primary mouse chondrocytes were treated with ER for in vitro assays. Furthermore, mice that underwent destabilization of the medial meniscus surgery were orally administered with ER. Western blotting suggested that ER increased protein expression of Nrf2 and HO-1 in primary chondrocytes and articular cartilage from knee joints. Cartilage damage in knee joints was significantly reduced by ER treatment. Western blotting and PCR analysis confirmed that ER could also suppress the expression of MMP-9 and MMP-13 in vivo and in vitro. The present findings suggested that ER effectively alleviated cartilage degradation and that activation of the Nrf2-heme oxygenase 1 pathway may play a role in ER-mediated cartilage protection against OA.

[PFNA and InterTAN intramedullary nailing in elderly patients with femoral intertrochanteric fractures: a Meta analysis].

OBJECTIVE: To evaluate the efficacy and safety of proximal femoral nail antirotation(PFNA) vs InterTAN nail in treating the elderly intertrochanteric femoral fractures. METHODS: Data of the randomized controlled trials(RCTs) about PFNA vs InterTAN for the treatment of the elderly intertrochanteric femoral fractures were searched in as the Cochrane Library, PubMed, EMbase, Wanfang, CNKI, CBM and VIP from their establishment to January 2018 for collecting. After study selection, assessment and data extraction conducted by two reviewers independently, meta-analyses were performed by using the RevMan 5.3 sofware. The level of evidence was assessed by using the GRADEpro system. RESULTS: Twelve studies involving 1 015 patients were included. The results of meta, analyses showed that: (1)safety indicator: compared with the InterTAN, PFNA had shorter operation time, and less intraoperative bleeding. But InterTAN had less total postoperative complications and internal fixation failure, but there was no significant difference in the operative incision lengths, fracture healing time and other postoperative complications. (2)efficacy indicator: compared with the InterTAN, the Harris hip score was lower after 3 months, but Harris hip score had no significant difference between the two groups after 6, 12 months. Based on GRADEpro system, all the evidence was at level C and weak recommendation(2C). CONCLUSIONS: The current evidence indicates that PFNA had a similar effect compared with the InterTAN. But InterTAN could provide better stability against rotation and axial pressure effect, can allow patients do functional exercise early such as ambulation to recovery the hip function. It also had less total postoperative complications and internal fixation failure for the poor quality of the original studies and the limited number of studies, a prudent choice is suggested and more high-quality, large-sample studies are need.

7,8-Dihydroxyflavone activates Nrf2/HO-1 signaling pathways and protects against osteoarthritis.

The aim of the present study was to investigate the effect of 7,8-dihydroxyflavone (7,8-DHF) against osteoarthritis (OA) and examine its regulatory role in the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in chondrocytes. Primary mouse chondrocytes were treated with 7,8-DHF to examine the expression of Nrf2 and downstream heme oxygenase 1 (HO-1). The surgical destabilization of the medial meniscus model was used to assess the effectiveness of 7,8-DHF in protecting the cartilage from damage, with knee cartilage harvested from mice for histological analysis. The results revealed that 7,8-DHF activated the Nrf2 signaling pathway in primary chondrocytes. Cartilage degradation in the 7,8-DHF-treated group was reduced significantly compared with that in the vehicle-treated group, according to histological evaluation. The gene expression of matrix metalloproteinase (MMP)1, MMP3, MMP13, interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α were reduced in the cartilage of OA mice following 7,8-DHF treatment. Genetic and protein analyses indicated that the expression levels of HO-1 were upregulated in the cartilage of the knee with OA, and 7,8-DHF treatment further promoted the induction of HO-1. These results suggest that 7,8-DHF may serve as a potential therapeutic agent in OA.

MMC controlled-release membranes attenuate epidural scar formation in rat models after laminectomy.

Epidural scar formation after laminectomy impede surgical outcomes of decompression. Mitomycin C (MMC) has been demonstrated to have significant inhibitory effects on epidural scar. This study was undertaken to develop an effective MMC controlled­release membrane and to investigate its effects on epidural scar in rat models of laminectomy. A total of 72 rats that underwent laminectomy were divided into three groups. Among them, 24 were treated with mitomycin C­polylactic acid (MMC-PLA) controlled­release membrane, 24 with mitomycin C-polyethylene glycol (MMC-PEG) controlled-release membrane, and no treatment was performed for the remaining 24 rats (control group). In the following 4 weeks, magnetic resonance image (MRI), macroscopic observation, histology and hydroxyproline (Hyp) concentration analysis were performed to explore the effects of these three therapies on epidural scar. MRI revealed a significant reduction of epidural fibrosis in MMC-PLA and MMC-PEG treatment groups, compared with the control group. Histological results also showed that collagen deposition was significantly reduced after being treated with MMC-PLA or MMC-PEG membranes. Likewise, Hyp concentrations of the epidural scar tissue in MMC-PLA and MMC-PEG groups were markedly lower than those in the control group. However, regarding the effects on reducing epidural scar, no significant difference was found between the MMC-PLA and MMC-PEG groups. In conclusion, MMC-PLA and MMC-PEG membranes are safe and effective in reducing fibrosis. Thus, MMC-controlled-release membranes promises to be a potential therapeutic in preventing epidural scar formation after laminectomy.