Jiao-Xiang Chen

Hydrogen sulfide protects against endoplasmic reticulum stress and mitochondrial injury in nucleus pulposus cells and ameliorates intervertebral disc degeneration

Graphical abstract Figure. No Caption available. Abstract It has been suggested that excessive apoptosis in intervertebral disc cells induced by inflammatory cytokines, such as interleukin (IL)‐1&bgr;, is related to the process of intervertebral disc degeneration (IVDD). Hydrogen sulfide (H2S), a gaseous signaling molecule, has drawn attention for its anti‐apoptosis role in various pathophysiological processes in degenerative diseases. To date, there has been no investigation of the correlation of H2S production and IVDD or of the effects of H2S on IL‐1&bgr;‐induced apoptosis in nucleus pulposus (NP) cells. Here, we found that the expression levels of cystathionine &bgr;‐synthase (CBS) and cystathionine &ggr;‐lyase (CSE), two key enzymes in the generation of H2S, were significantly decreased in human degenerate NP tissues as well as in IL‐1&bgr;‐treated NP cells. NaHS (H2S donor) administration showed a protective effect by inhibiting the endoplasmic reticulum (ER) stress response and mitochondrial dysfunction induced by IL‐1&bgr; stimulation in vitro, the effect was related to activation of the PI3K/Akt and ERK1/2 signaling pathways. Suppression of these pathways by specific inhibitors, LY294002 and PD98059, partially reduced the protective effect of NaHS. Moreover, in the percutaneous needle puncture disc degeneration rat tail model, disc degeneration was partially reversed by NaHS administration. Taken together, our results suggest that H2S plays a protective role in IVDD and the underlying mechanism involves PI3K/Akt and ERK1/2 signaling pathways‐mediated suppression of ER stress and mitochondrial dysfunction in IL‐1&bgr;‐induced NP cells.

A novel micro-CT-based method to monitor the morphology of blood vessels in the rabbit endplate

PurposeThe aim of this study was to develop a novel method for observing the morphology of the blood vessels in the rabbit endplate.MethodsTwenty 6-month-old rabbits were used in this study. The blood vessels in the L5 endplate in Group A were injected with iohexol and Group B with barium sulfate. Group C was the control group with saline. To optimize the study, Group B was divided into two subgroups: Group B-1 was injected with 100% (w/v) barium sulfate and Group B-2 with 50% (w/v). After injection, the L4–L5 vertebral body was excised and the cranial endplate of L5 was scanned using a micro-CT scanner. Models of the vertebral endplate and vessels were reconstructed using the 3D reconstruction software (Mimics 16.0) by calculating a bone threshold value, and then merged these two models to create a superimposed model.ResultsThe 3D vessel models could not be created in Groups A and C, but they were clearly visualized in Group B. In the 3D model, the blood vessels extended from the subchondral bone to the endplate, and the density of the blood vessels in the area of the nucleus pulposus (NP) was higher than in the annulus fibrosus.ConclusionsThe results of this study suggest that the blood vessels in the rabbit endplate can be clearly observed by the method described using barium sulfate [the 50% (w/v) gave better results compared with the 100% (w/v)]. The information from the 3D vessel structure could provide essential data to help us understand the nutrient pathways within the vertebral endplate.

A Computed Tomographic Morphometric Study of the Pediatric Occipital Bone Thickness: Implications for Pediatric Occipitocervical Fusion.

Study Design. This study is a computed tomographic-based morphometric analysis of the pediatric occipital bones as related to pediatric occipitocervical fusion. Objective. To quantify reference data concerning the thicknesses of the immature occipital bones to guide the pediatric occipitocervical fusion. Summary of Background Data. To the best of our knowledge, no published study has provided insight into the thicknesses of pediatric occiputs with different age groups. Methods. 80 pediatric patients were divided into 4 age groups, and their occiputs were studied on Philips Brilliance 256 iCT scan. Results. The mean thickness ± standard deviations of the pediatric occipital bones with different age groups is shown. The median and the paramedian regions are always thicker than the more lateral regions at each age group and the thickest point in the occiputs is mostly at the external occipital protuberance. The mean thickness of occiputs showed an obvious significant difference between each 2 age groups and no significant difference between male and female in different age groups except the group 4. Conclusion. Our investigation provides insight into the anatomy of occiputs in pediatric population and preoperative CT evaluation must be required to further decrease the risk of occipitocervical fusion. Level of Evidence: 2

The Impact of Facet Joint Violation on Clinical Outcomes After Percutaneous Kyphoplasty for Osteoporotic Vertebral Compression Fractures.

OBJECTIVE To determine whether the facet joint violation (FJV) impacts clinical outcomes after percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compression fractures. METHODS Patients undergoing bilateral PKP were enrolled and divided into FJV and non-FJV groups depending on their postoperative axial computed tomography scans. Radiologic parameters, visual analogue scale (VAS), and Oswestry Disability Index (ODI) scores were obtained preoperatively and each follow-up time postoperatively (1day, 1 week, 1 month, 3 months, 6 months, and 1 year). Finally, patient satisfaction surveys also were noted. RESULTS A total of 157 patients completed the 1-year follow-up. The incidence of FJV resulting from puncture trocars was 15.9% (25/157). Approximately 5.7% (9/157) and 10.2% (16/157) of patients were considered to have grade 1 and grade 2 violation, respectively. PKP decreased the VAS and ODI scores compared with the preoperative values in both groups. Patients with FJV had much greater VAS and ODI scores than did those without FJV at 1-day, 1-week, and 1-month follow-up. No significant differences were found between groups at 3-month, 6-month, and 1-year follow up. Patients in the FJV group were less satisfied with the surgical outcomes than were those without FJV at the last survey. CONCLUSIONS Approximately 15.9% of patients were diagnosed with FJV by postoperative computed tomography scans. FJV had a negative influence on clinical outcomes after PKP in osteoporotic vertebral compression fractures, primarily at short-term follow-up. In addition, FJV was also a risk factor in the long-term surgical satisfaction.

Polydatin suppresses nucleus pulposus cell senescence, promotes matrix homeostasis and attenuates intervertebral disc degeneration in rats

Abstract Intervertebral disc degeneration (IVDD) is one of the major causes of low back pain. Polydatin (PD) has been shown to exert multiple pharmacological effects on different diseases; here, we test the therapeutic potential of PD for IVDD. In in‐vitro experiments, we confirmed PD is nontoxic to nucleus pulposus cells (NPCs) under the concentration of 400 μmol/L. Furthermore, PD was able to decrease the level of senescence in TNF‐α‐treated NPCs, as indicated by β‐gal staining as well as senescence markers p53 and p16 expression. In the aspect of extracellular matrix (ECM), PD not only reduced metalloproteinase 3 (MMP‐3), metalloproteinase 13 (MMP‐13) and a disintegrin‐like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS‐4) expression, but also increased aggrecan and collagen II levels. Mitochondrion is closely related to cellular senescence and ECM homeostasis; mechanistically, we found PD may rescue TNF‐α‐induced mitochondrial dysfunction, and it may also promote Nrf2 expression and activity. Silencing Nrf2 partly abolished the protective effects of PD on mitochondrial homeostasis, senescence and ECM homeostasis in TNF‐α‐treated NPCs. Correspondingly, PD ameliorated IVDD in rat model by promoting Nrf2 activity, preserving ECM and inhibiting senescence in nucleus pulposus cells. To sum up, our study suggests that PD exerts protective effects in NPCs against IVDD and reveals the underlying mechanism of PD on Nrf2 activation in NPCs.

Parkin-mediated mitophagy as a potential therapeutic target for intervertebral disc degeneration

Intervertebral disc degeneration (IDD) is a complicated pathological condition blamed for low back pain. Mitochondrion is of vital importance for cellular homeostasis, and mitochondrial dysfunction is considered to be one of the major causes of cellular damage. Mitophagy is a cellular process to eliminate impaired mitochondria and showed protective effects in various diseases; however, its role in IDD is still not clear. Here, we explore the role of Parkin-mediated mitophagy in IDD. In this study, we found that Parkin was upregulated in degenerative nucleus pulposus (NP) tissues in vivo as well as in TNF-α stimulated NP cells in vitro. Knockdown of Parkin by siRNA showed that Parkin is crucial for apoptosis and mitochondrion homeostasis in NP cells. Further study showed that upregulation of Parkin by salidroside may eliminate impaired mitochondria and promote the survival of NP cells through activation of mitophagy in vitro. In in vivo study, we found that salidroside could inhibit the apoptosis of NP cells and ameliorate the progression of IDD. These results suggested that Parkin is involved in the pathogenesis of IDD and may be a potential therapeutic target for IDD.

Incidence and risk factors of facet joint violation following percutaneous kyphoplasty for osteoporotic vertebral compression fractures

Background Percutaneous kyphoplasty (PKP) has been widely used to osteoporotic vertebral compression fractures (OVCFs). No previous investigations have reported the incidence and risk factors of facet joint violation (FJV) caused by PKP. Purpose To determine the incidence and risk factors of FJV following PKP in patients with OVCFs. Material and Methods We reviewed a total of 153 patients who underwent bilateral PKP. Postoperative computed tomography (CT) scans were assessed to determine the degree of FJV owing to invasion by a puncture trocar. Clinical outcomes, including visual analogue scale (VAS) scores and Oswestry Disability Index (ODI) scores, were collected from all patients. Clinical and radiological data were analyzed to identify the risk factors for FJV. Results FJV caused by PKP affected 18.9% of patients and 9.6% of facet joints; approximately 3.9% and 5.7% of facet joints were considered to have grade 1 and grade 2 violations, respectively. There were significant differences between the FJV and non-FJV groups in VAS and ODI scores after surgery. Significant differences were found with respect to the facet joint angle (FJA), the pedicle diameter (PD), and the distance from the entry point to the facet joint space (DEF). Multiple logistic regression analysis indicated that an FJA > 55°, a PD < 5 mm, and a DEF < 5 mm were independent risk factors for FJV. Conclusion The placement of a puncture trocar can cause FJV in patients with OVCFs and impact clinical outcomes after PKP. Special attention should be given to patients with an FJA > 55°, a PD < 5 mm, and a DEF < 5 mm.

Changes in Pelvic Incidence, Pelvic Tilt, and Sacral Slope in Situations of Pelvic Rotation.

Study Design: Digitally reconstructed radiograph-based study. Objective: Using a computer-based method to determine what degree of pelvic rotation is acceptable for measuring the pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). The effectiveness of a geometrical formula used to calculate the angle of pelvic rotation proposed in a previous article was assessed. Summary of Background Data: It is unclear whether PI, PT, and SS are valid with pelvic rotation while acquiring a radiograph. Materials and Methods: Ten 3-dimensionally reconstructed models were established with software and placed in a neutral orientation to orient all of the bones in a standing position. Next, 140 digitally reconstructed radiographs were obtained by rotating the models around the longitudinal axis of each pelvis in the software from 0 to 30 degrees at 2.5-degree intervals. PI, PT, and SS were measured. The rotation angle was considered to be acceptable when the change in the measured angle (compared with the “correct” position) was <6 degrees. The rotation angle (&agr;) on the images was calculated by a geometrical formula. Consistency between the measured value and the set angle was assessed. Results: The acceptable maximum angle of rotation for reliable measurements of PI was 17.5 degrees, and the changes in PT and SS were within an acceptable range (<6 degrees) when the pelvic rotation increased from 0 to 30 degrees. The effectiveness of the geometrical formula was shown by the consistency between the set and the calculated rotation angles of the pelvis (intraclass correlation coefficient=0.99). Conclusions: Our study provides insight into the influence of pelvic rotation on the PI, PT, and SS. PI changes with pelvic rotation. The acceptable maximum angle for reliable values of PI, PT, and SS was 17.5 degrees, and the rotation angle of the pelvis on a lateral spinopelvic radiograph can be calculated reliably.

A Method to Prevent Occipitocervical Joint Violation Using Plain Radiography During Percutaneous Anterior Transarticular Screw Fixation.

Study Design. A prospective study of anterior transarticular screw (ATS) fixation patients. Objective. To develop a method to determine screw tip position through plain radiography after percutaneous ATS fixation to prevent occipitocervical joint (OCJ) violation. Summary of Background Data. No studies using plain radiography to prevent OCJ violation during percutaneous ATS fixation have been performed. Methods. In total, 34 subjects (with 68 screws) who had undergone percutaneous ATS fixation were enrolled. To evaluate the screw tip location in relation to the C1 lateral mass (LM), the screw tip positions were graded 1, 2, or 3 on anteroposterior (AP) radiographs, and I, II, or III on lateral radiographs. OCJ violation was analyzed by postoperative computed tomography (CT). Results. Screws with tips located lower (tip I) in the LM did not result in OCJ violation. Only one tip in the tip 3 position showed OCJ perforation, and this screw was also located in tip III. Screw perforation rates of tip 1–tip II, tip 1–tip III, and tip 2–tip III were the highest (100%), followed by tip 2–tip II (10.5%) and tip3–tip III (10%). Conclusion. This study provides insights into OCJ violation during percutaneous ATS fixation. According to AP radiography, a percutaneous ATS with the screw tip located in the lateral part of the LM resulted in a lower rate of OCJ perforation, whereas screws located in the medial LM resulted in the highest rate of perforation. Percutaneous ATS with the screw tip located in the neutral part of the LM should ensure that the screw tip is below the upper part of the LM, preventing OCJ violation. These findings may help surgeons assess screw positioning both during and after the operation. Level of Evidence: 3