Icariin regulates stem cell migration for endogenous repair of intervertebral disc degeneration by increasing the expression of chemotactic cytokines.

BACKGROUND: Icariin (ICA) can promote the migration and bone formation of bone marrow mesenchymal stem cells. This study explored a potential role of ICA in recruiting stem cell niches (SCNs) within the intervertebral disc region (ISN)-derived stem cells (ISN-SCs) to treat intervertebral disc degeneration (IVDD). MATERIALS AND METHODS: EdU staining, transwell, and wound healing tests were used to analyze the function of ICA on ISN-SCs proliferation and migration ability. Simultaneously, the IVDD rat model was constructed by the acupuncture and divided into Sham, Sham + ICA, IVDD, and IVDD + ICA groups. H&E and PAS staining were performed to detect the pathological changes of IVDD tissues. Immunofluorescence was performed to discover relevant marker expression on the surface of stem cells in the IVDD tissues. Western blot and qPCR were executed to find the protein and mRNA expression of related cytokines in the IVDD tissues. RESULTS: ISN-SCs treated with 1 µM ICA obtained the better ability of proliferation and migration. H&E staining showed that the annulus fibrosus in the IVDD group was obviously hyperplasia with cavities and fissures; the nucleus pulposus was reduced. PAS staining showed that the content of polysaccharides was significantly reduced in the nucleus pulposus of IVDD group. However, the ICA treatment alleviated the pathological trends of the IVDD tissues. Simultaneously, ICA treatment increased significantly the expression of stem cells and IGF-1, TGF-ß, SDF-1, CCL-5, Collagen I, Collagen II, Aggrecan, and SOX9 in IVDD tissues. CONCLUSIONS: ICA treatment promoted the migration of stem cell in IVDD by increasing the expression of chemotactic cytokines, including IGF-1, TGF-ß, SDF-1, and CCL-5.

Evaluation of the analgesic effect of vertebral cancellous bone infiltration anaesthesia during vertebroplasty.

OBJECTIVE: To evaluate the analgesic effect of vertebral cancellous bone infiltration anaesthesia during percutaneous vertebroplasty (PVP). METHODS: Patients treated with vertebral cancellous bone infiltration anaesthesia (intervention group) or local anaesthesia alone (control group) during PVP at our institution during 2016-2018 were reviewed. The visual analogue scale (VAS) score before the operation, during establishment of the puncture channel, during pressure changes in the vertebral body (e.g., when removing or inserting pushers or needle cores), during bone cement injection, immediately after the operation, and at 2 h and 1 day postoperatively were compared between the groups. The patient's satisfaction with the operation was recorded and compared between groups. RESULTS: A total of 112 patients were enrolled (59 cases in the intervention group and 53 cases in the control group). There was no difference in the VAS score between the groups before the operation or during establishment of the intraoperative puncture channel (P > 0.05). The VAS score in the intervention group was significantly lower than that in the control group during pressure changes in the vertebral body (removal or insertion of puncture needle cores or pushers) and bone cement injection (P < 0.05). Immediately after the operation and at 2 h postoperatively, the pain in the intervention group was also significantly lower than that in the control group (P < 0.05), but there was no significant difference between the groups at 1 day postoperatively (P > 0.05). The patient satisfaction rate was 88% (52/59) in the intervention group and 67% (35/53) in the control group (P < 0.05). CONCLUSIONS: Vertebral cancellous bone infiltration anaesthesia may effectively relieve intraoperative pain and improve the surgical experience of patients without affecting the clinical effect of surgery.

Effect of time to first ambulation on recurrence after PELD.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the effect of time to first ambulation on recurrence after percutaneous endoscopic lumbar discectomy (PELD). METHODS: From July 2017 to August 2018, 90 patients with lumbar intervertebral disc herniation underwent PELD surgery. According to the initial walking time, i.e., the time until the patient could walk after the operation, the operations were divided into three groups: early stage, middle stage, and late stage. The follow-up period was 3 months, and complete follow-up data were obtained. The visual analog scale (VAS) and Oswestry disability index (ODI) scores before the operation, at first ambulation, 1 month after the operation, and 3 months after the operation and the recurrence and incidence rates of high magnetic resonance imaging (MRI) signal in the vertebral endplate area were recorded after the operation. RESULTS: The success rate was 100% for these 90 cases. The VAS and ODI scores at the first ambulation after the operation significantly improved compared with those before the operation, and the difference was statistically significant. The improvements in the lumbar VAS and ODI scores of the middle- and late-stage groups were better than that of the early-stage group at 1 and 3 months after the operation, and the differences were statistically significant; however, there was no significant difference between the middle- and late-stage groups. The postoperative recurrence rate and rate of high MRI signal in the vertebral endplate area were significantly higher in the early-stage group than in the other two groups, and the difference was statistically significant. CONCLUSION: The time to first ambulation after PELD is an important factor affecting the curative effect of the operation. Early ambulation may be one of the factors affecting recurrence after PELD.

A second puncture and injection technique for treating osteoporotic vertebral compression fractures.

OBJECTIVE: To evaluate the clinical effect of the second puncture and injection technique during a percutaneous vertebroplasty (PVP) procedure. METHODS: Patients treated with a second puncture and injection (group A) or a single puncture and injection (group B) during PVP at our institution during 2010-2017 were reviewed. Vertebral height loss, visual analogue scale (VAS) score, Oswestry disability index (ODI), adjacent vertebral fractures, and cement leakage were compared between the groups. RESULTS: A total of 193 patients were enrolled (86 cases in group A, 107 cases in group B). The follow-up period was 15.64 (12-20) months. The loss of anterior (group A 0.01 ± 0.03; group B 0.14 ± 0.17) and middle (group A 0.13 ± 0.12; group B 0.16 ± 0.11) vertebral height in group B was significantly higher than that in group A (P < 0.05). The VAS score and ODI were also significantly higher in group B than in group A at the final follow-up; the VAS score and ODI in group B were 1.65 ± 0.70 and 14.50 ± 4.16, respectively, and those in group A were 1.00 ± 0.74 and 12.81 ± 4.02, respectively (P < 0.05). Three patients in group A and two in group B experienced adjacent vertebral fractures. Regarding mild, moderate, and severe cement leakage, there were 25 (29%), 5 (5%), and 0 cases, respectively, in group A and 28 (26%), 3 (2.8%), and 1 (0.009%) case, respectively, in group B (P > 0.05). CONCLUSIONS: The second puncture and injection technique may effectively increase the dispersion of cement, thus preventing recompression of the cemented vertebral body, and it does not increase the risk of cement leakage or adjacent vertebral fracture.

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.