The mechanism of TDP-43 gene expression on inflammatory factors and the JNK and p38 MAPK signalling pathways in ischaemic hypoxic stress dependence.

In this study, the mechanism of TDP-43 gene expression on inflammatory factors and Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signalling pathways in ischaemic hypoxic stress dependence was investigated. Sixty SD rats were selected and divided into the control group, the osteoarthritis (OA) model group, and the TDP-43-mMSCs+OA group. In the OA model group and the TDP-43-mMSCs+OA group, OA was established by collagenase injection. Western blotting assays were used to detect the expression of TDP-43 in cartilage tissues of each rat. The secretion of tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in the serum of rats was determined by enzyme-linked immunosorbent assay (ELISA). The formation of cytoplasmic stress granules (SGs) and the expression of receptor for activated c-kinase 1 (RACK1) were detected by Western blotting assays in each group of rats. The expression of MTK1 and MAPKKK phosphorylation and changes in the JNK and p38 MAPK signalling pathways were detected by Western blotting assays. Compared with the control group, the expression of TDP-43 in the cartilage tissue of rats in the OA model group was significantly decreased. The expression of TDP-43 in the cartilage tissue of rats in the TDP-43-mMSCs+OA group was significantly higher than that of the control group and the OA model group, which indicates that TDP-43-mMSC transplantation was successful. Enzyme-linked immunosorbent assay results showed that the plasma TNF-α and IL-1ß levels in the OA model group were significantly increased (P < 0.01) when compared with the control group. However, the secretion of TNF-α and IL-1ß in the serum of the TDP-43-mMSCs+OA group was significantly lower than that of the model group (P < 0.01) but still higher than the control group. This indicates that overexpression of TDP-43 reduces the inflammatory response induced by OA. Western blotting assays showed that the amount of cytoplasmic SGs in the cartilage tissue of rats in the OA model group was significantly decreased when compared with the control group. The amount of SGs in the cartilage of rats in the TDP-43-mMSCs+OA group was significantly higher than that of the model group. The expression of RACK1 in the cartilage tissue of rats in the OA model group was significantly higher than that of the control group. Overexpression of the TDP-43 gene can interfere with the secretion of inflammatory factors and inhibit the activation of the JNK and p38 MAPK signalling pathways by ischaemic hypoxia stress. Thus, the molecular mechanism of chondrocytopathic lesions was reversed, which provided a new theoretical basis for the treatment of OA.

Icariin inhibits chondrocyte apoptosis and angiogenesis by regulating the TDP-43 signaling pathway.

BACKGROUND: This study focused on the mechanisms where icariin inhibited chondrocyte apoptosis and angiogenesis by regulating the TDP-43 signaling pathway. METHODS: A rat osteoarthritis (OA) model was established by collagenase injection. Histological examination of the articular cartilage and synovial tissue was performed 6 weeks after operation. Cartilage cell line overexpressing TDP-43 and mesenchymal stem cell line (TDP43-MSCs) of the rat TDP43 gene were established. RESULTS: In OA rats transplanted with TDP43-mMSCs, TDP43 was highly expressed in chondrocytes (TDP43-HC), while TDP43 expression was low in HC and MSCs-HC (p < 0.05). After the intervention of MSCs-TDP43, high expression of TDP43 induced the apoptosis and death of chondrocytes. After the addition of icariin, late apoptosis and death of TDP43-HC were significantly attenuated. Apoptosis and death of HC, MSCs-HC, and TDP43-HC cells were effectively controlled with icariin, and no apparent cell death was found. ELISA showed that the VEGF and HIF-1 alpha were significantly higher in the rat OA model than the normal control rats. CONCLUSION: TDP43-MSC transplantation interfered with the expression of TDP43 in the articular chondrocytes of OA rats, which may impact on inducing apoptosis of chondrocytes as well as inhibiting the proliferation of chondrocytes. Additionally, TDP43-MSCs appeared to promote the formation of neovascularization in the synovial tissue, which could be significantly attenuated by icariin.

Ultra-early injection of low-viscosity cement in vertebroplasty procedure for treating osteoporotic vertebral compression fractures: A retrospective cohort study.

OBJECTIVE: To evaluate the clinical effect of ultra-early injection (before the phase of "tooth-paste-like") of low-viscosity cement in percutaneous vertebroplasty (PVP) for treating osteoporotic vertebral compression fractures (OVCFs). METHODS: Two hundred sixty-one patients who had PVP procedures with low-viscosity cement (ultra-early injection: 145, normal injection: 135) were included from July 2010 to July 2016 in our hospital. Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Cobb angle, cement leakage, and adjacent vertebral fractures were evaluated. The follow-up period was over 12 months. RESULTS: VAS 3.0 d after surgery was significantly reduced in the ultra-early injection group compared to that in the control group (P = 0.00), but no difference was found at the final follow-up (P = 0.53). Similar results were found for ODI. The Cobb angle in both groups was recovered after PVP (P < 0.05); however, in the control group, the Cobb angle at the final follow-up was significantly increased compared with that 3.0 d after surgery (P = 0.00). There was a significant difference in the Cobb angle between the two groups at the final follow-up (P = 0.00). Regarding cement leakage, there were no significant differences in terms of mild (P = 0.58), moderate (P = 0.68), or severe leakage (P = 0.52). Seven patients in the control group had adjacent vertebral fractures, but only one patient in the ultra-early injection group experienced adjacent fractures (P = 0.03). CONCLUSIONS: Ultra-early injection of low-viscosity cement during PVP procedures in the treatment of OVCFs not only quickly and significantly relieves pain, reduces the incidence of adjacent vertebral fractures, and prevents progressive kyphotic deformity, but also does not increase the risk of cement leakage when compared with that of the traditional injection procedure.

Efficacy of different treatment modalities and the influence on PEDF and VEGF in patients with neovascular glaucoma in high altitude area / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical efficacy of different treatment modalities and the influence on the levels of pigment epithelium-derived factor ( PEDF ) and vascular endothelial growth factor ( VEGF ) in patients with neovascular glaucoma ( NVG) in high altitude area.?METHODS: Ninety cases of patients ( 90 eyes ) with NVG treated in our hospital were selected as the study objects, and they were divided into Group A and Group B according to different surgery methods, 45 cases in each groups. Group A was given Ex-press glaucoma drainage device implantation, and Group B was given trabeculectomy combined with cyclocryotherapy. We observed the clinical efficacy, intraocular pressure and visual acuity in the two groups, detected the PEDF and VEGF levels in the aqueous humor, and recorded the postoperative complications.?RESULTS:The total effective rate of Group A was 91％, significantly higher than that of Group B 76％ (P<0. 05). At 2wk, 2 and 4mo after surgery, IOP levels were significantly lower than that before surgery (P<0. 05), and those in Group A were significantly lower than those in Group B (P<0. 05). There was no significantly difference in IOP levels at 6mo after surgery between the two groups (P>0. 05). At 1wk after operation, the incidence of visual reduction in Group A was 7％, significantly lower than that in Group B 22％ (P<0. 05). At 1wk after operation, PEDF levels were significantly higher than those before operation in the two groups (P<0. 05), and that in Group A was significantly higher than that in Group B (P<0. 05);VEGF levels were significantly lower than that before operation in the two groups (P<0. 05), and that in Group A was significantly lower than that in Group B (P<0. 05). The incidence rate of complications in Group A was 4％, significantly lower than that of 18％ in Group B at 6mo postoperatively (P<0. 05).?CONCLUSION: Ex- press glaucoma drainage device implantation, trabeculectomy combined with cyclocryotherapy can both be used to treat patients with NVG in high altitude area. But the former can effectively maintain visual acuity, and improve PEDF and VEGF levels in aqueous humor, with fewer complications and more accurate curative effect.