Objective. Trans-cinnamaldehyde (TCA), a compound from Cinnamomum cassia Presl, has been reported to have anti-inflammatory effect. However, its effect on cartilage degradation in osteoarthritis is unclear. This study is designed to examine the effects of TCA on cartilage in vitro and in vivo. Material and Methods. SW1353 cells and human primary chondrocytes were treated with varying concentrations of TCA (2-20 μg/ml) for 2 h followed by IL-1β stimulation. Cell viability was examined by the MTT assay. Expression of MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 was examined by Western blot and RT-qPCR. Monosodium iodoacetate (MIA)-induced OA was established in rats to assess the chondrocyte protective effects of intraperitoneal injection of TCA (50 mg/kg). Results. TCA at a concentration of 10 μg/ml had no significant effect on cell viability. MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 were decreased by TCA 2-10 μg/ml in a dose-dependent manner (all P<0.05). Pretreatment with TCA decreased the degradation of IκBα and increased the expression of p-IκBα, indicating that NF-κB inactivation was induced by TCA in IL-1β-stimulated SW1353 cells. Pretreatment with TCA decreased the levels of p-p38 and p-JNK, while the levels of p-ERK were not significantly affected. TCA 10 μg/ml significantly decreased expression levels of MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5. In vivo results showed that TCA alleviated cartilage destruction and the OARSI scores. Conclusion. TCA possesses anti-inflammatory effect in vitro and exerts chondrocyte protective effects in vivo, in which NF-κB and p38-JNK were involved.
Background: To investigate the mechanism underlying the chondroprotective effect of estrogen in AMPactivated protein kinase (AMPK) deficiency mice. Methods: Female cartilage-specific AMPKα double knockout (AMPKα cDKO) mice were generated and subjected to ovariectomy (OVX). The model of osteoarthritis (OA) was induced by destabilization of medial meniscus (DMM). Histopathological changes were evaluated by using OARSI scoring systems. Autophagy changes were analyzed by immunofluorescence staining. Human chondrocytes were subjected to mechanical stress to mimic OA development. and incubated in presence of or absence of 17β-estradiol or/and compound C (AMPK inhibitor) or/and U0126 (ERK inhibitor). The expression levels of ERK1/2 phosphorylation, p70S6K phosphorylation and light chain 3 (LC3) were detected by Western blot. Results: Compared with in OVX-sham AMPKα cDKO and OVX-sham WT mice, DMM-induced OA is more severe, and significantly low level of LC3 was observed in articular cartilage in OVX AMPK cDKO mice. Both mechanical stress and compound C were shown to induce an increase in phosphorylation of p70S6K, respectively. 17β-estradiol stimulation led to a reduction in the basal level of p70S6K phosphorylation as well as in the compound C or mechanical stress-induced level of p70S6K phosphorylation. 17β-estradiol stimulation not only led to an increase in LC3 conversion but also overrode the inhibitory effect of compound C on LC3 conversion. The effects of 17β-estradiol were abrogated by blocking ERK signaling pathway. Conclusions: Our findings suggest that estrogen can protect articular cartilage from damage during OA development by promoting chondrocyte autophagy via ERK-mammalian target of rapamycin (mTOR) signaling, and give new insight into the mechanism of the chondroprotective effect of estrogen.
Background: Intraarticular injection of the mesenchymal stem cells (MSCs) has shown to be successful for treating osteoarthritis (OA). Nevertheless, many studies have been focusing on autologous MSCs. The following study investigates the safety and effectiveness of intraarticular injection of allogenic MSCs in a pig OA model. Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were labelled with bone marrow-derived mesenchymal stem cells (BM-MSCs) to allow cells tracking using magnetic resonance imaging (MRI). A pig OA model was established by bilateral medial meniscectomy. Next, SPIO-BM-MSCs were injected into the right knee, while the left knee was left untreated. MRI and radiography were used to assess the degree of OA and to evaluate the effectiveness of allogenic MSCs. Hematoxylin and eosin (H&E), safranin-o fast green staining, toluidine blue, and immunohistochemical staining were used to evaluate the therapeutic effect of the injections. Results: At concentration of ≤20 μg/mL, SPIO caused no toxicity to BM-MSCs. Four weeks after surgery, OA changes were observed on MRI scan. The SPIO labeled BM-MSCs were found moving towards the impaired part of the cartilage 8 to 24 h after injections. In addition, no significant differences between the right side (therapeutic side) and the left side (untreated side) were observed following histological and immunohistochemistry analysis. Conclusions: The suitable concentration of SPIO for labelling BMSCs was 20 μg/mL, while the allogenic MSCs could move towards and accumulate around the impaired cartilage. No significant difference was found between treatment and control group.
Hip preserving procedures are still a challenge in late-stage osteonecrosis of femoral head (ONFH) patients. We aimed to compare the clinical outcomes of surgical dislocation and impaction bone graft and surgical dislocation and rotational osteotomy for treatment of ONFH in Association Research Circulation Osseous (ARCO) stage III patients. We retrospectively reviewed 30 ARCO stage III patients (33 hips) who had surgical dislocation and impaction bone graft or surgical dislocation and rotational osteotomy in our center from June 2012 to December 2017. Baseline characteristics, clinical evaluation using Harris score and radiologic evaluation up to 12 months after surgery were recorded and compared. Fifteen patients (17 hips) were in the surgical dislocation and impaction bone graft group and 15 patients (16 hips) were in the surgical dislocation and rotational osteotomy group. No significant differences in age, gender, etiology, ARCO stage, duration of illness, operation time, and length of hospitalization were observed between the 2 groups. Compared to preoperation Harris score, the Harris score of 6 months postoperation and 12 months postoperation significantly improved. At 12 months postoperation, the excellent and good rate was 76.5% in the impaction bone graft group and 87.5% in the rotational osteotomy group. No significant difference in Harris scores was detected in the 2 groups. Surgical dislocation and impaction bone graft and surgical dislocation and rotational osteotomy had satisfactory 1-year efficacy for ARCO III ONFH patients. Surgical dislocation and rotational osteotomy had better short-term efficacy than surgical dislocation and impaction bone graft.
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