Sinapic Acid Inhibits IL-1ß-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration.

BACKGROUND: Low back pain (LBP) is a very common condition and leads to serious pain, disability, and price tag all over the world. Intervertebral disk degeneration (IDD) is one of the major reasons that contributed to LBP. The levels of interleukin 1 beta (IL-1ß) increase significantly in degenerative disks. IL-1ß also accelerates IDD. Sinapic acid (SA) has the effect of anti-inflammatory, antioxidant and antimicrobial. However, the effect of SA on IDD has never been studied. Therefore, the aim of this study was to figure out whether SA has protective effect on nucleus pulposus (NP) cells and further explore the possible underlying mechanism. METHODS: The nucleus pulposus (NP) tissues of rats were collected and cultured into NP cells. The NP cells were stimulated by IL-1ß and treated with SA. In vitro treatment effects were evaluated by ELISA, Western blot assay, immunofluorescence, TUNEL method and real-time PCR. We conducted percutaneous needle puncture in the rat tail to build intervertebral disk degeneration model and treated rats with SA. In vivo treatment effects were evaluated by hematoxylin and eosin (HE) and safranin O (SO) staining and magnetic resonance imaging (MRI) method. RESULTS: Our results showed that SA not only inhibited apoptosis but also suppressed inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in IL-1ß-stimulated NP cells. As to extracellular matrix (ECM), SA could increase collagen II and aggrecan levels and reduce the expression of MMP13 and ADAMTS5 during the stimulation of IL-1ß. Furthermore, SA could activate nuclear factor-erythroid 2-related factor-2 (Nrf2) to inhibit nuclear factor κB (NF-κB) induced by IL-1ß. Nrf2 knockdown partly reduced the protective effect of SA on NP cells. Correspondingly, SA ameliorated IDD by promoting Nrf2 expression. In vivo results also showed that SA could delay the progression of IDD. CONCLUSION: In conclusion, we demonstrated that SA could protect the degeneration of NP cells and revealed the underlying mechanism of SA on Nrf2 activation in NP cells.

The compression of L5 nerve root, single or double sites?-radiographic graded signs, intra-operative detect technique and clinical outcomes.

BACKGROUND: The L5 nerve root could be compressed at both L4-5 and L5-S1 regions. If L5 nerve root has confirmed compression at L4-5 level and questionable compression at L5-S1 foramina, performing both surgeries at L4-5 and L5-S1 levels may induce unnecessary extra surgery on L5-S1; however, ignoring foraminal stenosis of L5/S1 may require re-exploration. METHODS: Two hundred seventeen patients with L5 nerve root compressed at L4-5 lateral access were performed with L4-5 decompression and interbody fusion. Lee et al. grade classification was used to assess the foraminal stenosis of L5-S1 preoperatively. Nerve root probe was designed and used to detect if there were foraminal stenosis at L5-S1 level that compressing the exiting L5 nerve root. Visual analog scale (VAS) of low back pain, leg pain and Oswestry Disability Index (ODI) were used to assess clinical outcomes. RESULTS: For all of 217 patients who underwent L4-5 surgery, L5-S1 foramina were preoperatively assessed as: grade 0: 125 cases, grade 1: 58 cases, grade 2: 23 cases, and grade 3: 11 cases. After intra-operative L5 nerve root detection, 11/11 patients with grade 3 radiographic foraminal stenosis, 6/23 (26.1%) with grade 2 and 2/58 (3.4%) who had grade 1 underwent L4-5 and L5-S1 transforaminal lumbar interbody fusion (TLIF), the others received only L4-5 TLIF. Compared to pre-operative baseline data, both L4-5 TLIF and L4-5 and L5-S1 TLIF groups had significant decreased VAS of low back pain and leg pain, and ODI at 3 and 24 months after operation. CONCLUSIONS: We suggested that our novel nerve root probe combined with pre-operative radiographic grade may be helpful to surgeons to identify the single or double compression of L5 nerve root and make a more precise surgical strategy to improve surgical outcome than the method depended on pre-operative radiographic grade alone.

Correlation between lumbar intervertebral disc height and lumbar spine sagittal alignment among asymptomatic Asian young adults.

BACKGROUND: To investigate the distribution and characteristics of the lumbar intervertebral disc height (IDH) in asymptomatic Asian population and to determine whether the lumbar IDH is related to the lumbar spine sagittal alignment. METHODS: A cohort of 169 cases of asymptomatic volunteers was enrolled from January 2014 to July 2016. All participants underwent magnetic resonance imaging of the lumbar spine and panoramic radiography of the spine. Panoramic radiographs of the spine were taken to evaluate pelvic incidence (PI), sacral slope (SS), and pelvic tilt (PT) using Surgimap® software. Roussouly classification was utilized to categorize all subjects according to the four subtypes of sagittal alignment. The IDH was measured on the MRI mid-saggital section of the vertebral body. The relationships between lumbar IDH and spine-pelvic parameters were also assessed using the Spearman correlation analysis. RESULTS: The reference value ranges of IDH in asymptomatic Asian volunteers between L1/2, L2/3, L3/4, L4/5, and L5/S1 were (6.25, 10.99), (6.97, 12.08), (7.42, 13.3), (7.76, 14.57),and (7.11, 13.12) mm, respectively. Based on the above reference value, the high lumbar intervertebral space is defined as more than 14 mm. According to the Roussouly Classification, there are 33 cases in type I, 48 in type II, 66 in type III, and 22 in type IV. According to the definition of the high IDH, there are two cases in type I, three in type II, nine in type III, and eight in type IV. The results indicated that people in the Roussouly III and IV subtypes had greater values for IDH compared to those of Roussouly I and II subtypes, and the spinopelvic parameters were partly correlated with IDH in different subtypes. In addition, levels L4-L5 showed the highest IDH for all four groups followed by the L3-L4 and L5-S1 levels, and the value of L3-L4 is equivalent to that of L5-S1. All type groups showed moderate and positive correlations between the PI and IDH except the level of L1-L2 in type IV. CONCLUSIONS: The IDH may influence the lumbar spine sagittal alignment in asymptomatic Asian adults. Moreover, pre-operative evaluation of IDH is useful for selection of optimal cage size and reconstruction of spinal alignment.

NELL-1 based demineralized bone graft promotes rat spine fusion as compared to commercially available BMP-2 product.

BACKGROUND: Spinal fusion is among the most commonly performed orthopaedic procedures. Unfortunately, current treatments such as autologous bone grafting or recombinant proteins (BMP-2) have numerous clinical shortcomings. Here, we directly compare the efficacy of NELL-1, a novel osteoinductive growth factor, to two currently available treatments, (1) recombinant BMP-2 and (2) iliac crest bone grafting, in a spinal fusion model. METHODS: Twenty-six skeletally mature athymic rats underwent posterolateral spine fusion of L4/L5 vertebrae. Treatment groups included NELL-1 (10 and 50 µg) in a demineralized bone matrix (DBX), as compared to BMP-2 (90 µg) in an absorbable collagen sponge (ACS) or morselized iliac crest bone. Scaffolds without recombinant protein were used as controls. Animals were sacrificed at 4 weeks post-operative and fusion was assessed by manual palpation, radiography [high-resolution X-ray, micro-computed tomography (microCT)], histology (hematoxylin and eosin, Masson's trichrome) and immunohistochemistry (osteocalcin). RESULTS: Results showed 100 % fusion in all NELL-1- and BMP-2-treated samples. In contrast, lower rates of fusion were observed in scaffold-only and bone graft treatment groups. MicroCT scans revealed radiographic evidence of fusion among spines treated with NELL-1. Bone bridging was also observed with BMP-2 treatment, but was accompanied by inner radiolucency, suggesting cyst-like bone formation. Histologically, NELL-1-treated grafts showed increased bone formation, endochondral ossification and vascularization. Although BMP-2 treated grafts exhibited increased bone formation and angiogenesis, numerous adipocytes were also observed. CONCLUSION: NELL-1-based bone grafts are comparable to BMP-2 + ACS in spinal fusion efficacy. Histological differences were observed however, including robust endochondral ossification with NELL-1 treatment as compared to lipid-filled bone with BMP-2 treatment. These findings suggest NELL-1 based bone grafts show promise for future efforts in skeletal tissue engineering.

[Clinical characteristics and results of cervical spinal cord injury in the patients with ossification of the posterior longitudinal ligament].

OBJECTIVE: To investigate the clinical characteristics and results of cervical spinal cord injury (SCI) in the patients with ossification of the posterior longitudinal ligament (OPLL). METHODS: Nineteen patients with cervical SCI associated with OPLL were retrospectively analyzed. Data collection included: pre- and postoperative neurological function, OPLL-type, MRI signal changes and surgical approaches. RESULTS: Spinal cord associated with OPLL was injured severely by mild trauma. Methylprednisolone sodium succinate was used within 8 h after trauma in 12 cases. Two of them died of complications. The neurological functions were markedly improved in the other 10 cases. Seventeen cases had surgical treatment. The neurological functions (Frankel grade) were improved significantly in the operated patients except for one, who died 27 d after operation. CONCLUSIONS: The patients with OPLL are prone to have severe SCI, which directly associates with the preexisting OPLL-type and hyper-intensity signal change in the spinal cord on MRI. Both of using methylprednisolone sodium succinate administration within 8 h after trauma and surgical decompression may improve the neurological outcomes.