Search

Objective: Unilateral biportal endoscopic discectomy (UBE) is an emerging and minimally invasive surgeryfor lumbar spinal degenerative disease. However, the efficacy, safety and the radiological changes of dural sac and paraspinal muscle of UBE compared with the conventional percutaneous transforaminal endoscopic discectomy (PTED) remains to be determined. The purpose of the study was to comprehensively compare the clinical efficacy between UBE and PTED in the surgical treatment of lumbar spinal degenerative disease., Methods: The clinical and radiological data of patients who underwent single-segment endoscopic surgery for lumbar spinal degenerative disease in our hospital from January 2021 to June 2022 were collected in the retrospective study. The visual analogue score (VAS) for back and leg pain, Oswestry disability index (ODI) before and 3, 6, and 12 months postoperative, changes of the cross-sectional area of the dural sac area and paraspinal muscles on axial T2-weighted MRI, operation time, intraoperative complications, MacNab criteria for evaluating efficacy at 12 months postoperatively, and recurrence rate of symptoms within 12 months were compared between patients undergoing PTED and UBE surgeries., Results: A total of 142 patients were included. Among them 74 patients underwent PTED surgery, and 68 patients underwent UBE surgery. No statistically significant differences were identified between the groups in demographic variables. The average VAS and ODI scores in both groups showed significant improvement during the follow-up but without statistically significant difference between the groups. The average operation time in the PTED group was 74.82 ± 19.49 min shorter than the 81.36 ± 21.37 min in the UBE group, exhibiting no statistically significant difference. Although the incidence of complications and recurrence was lower in the UBE group (4.05% vs. 1.47%, p = 0.354; 4.05% vs. 1.47%, p = 0.354, respectively), these differences did not reach statistical significance. The dural sac area in the PTED group increased byan average of 43.16 ± 14.62 cm 2 , and it was 68.53 ± 16.42 cm 2 in the UBE group. Despite the dural sac area increased in both groups, the UBE group had a statistically significant greater improvement than the PTED group (p = 0.000). The area of the paraspinal muscle in the UBE group was significantly greater postoperatively (34.54 ± 2.75 cm 2 vs. 36.22 ± 2.96 cm 2 , p = 0.001) and significantly less than in the PTED group at 12 months postoperatively (31.17 ± 2.59 cm 2 vs. 29.46 ± 3.11 cm 2 , p = 0.001)., Conclusion: Both PTED and UBE surgeries can achieve satisfactory improvement in symptoms and function for patients with lumbar spinal degenerative disease and can be well-maintained as a first-line minimally invasive treatment. However, the UBE technique can achieve a better decompression area to restore the normal shape of the dural sac but may lead to greater paraspinal muscle damage and atrophy., (© 2025 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma., Competing Interests: Da-Fu Chen is an editorial board member for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2024 The Authors.)

Study Design: Retrospective study., Objective: Our purpose was to evaluate spinal rotation measurement by scoliometer or EOS Imagings with reference to that by CT images, and to clarify their applicability in clinical practice., Methods: Patients with adolescent idiopathic scoliosis (AIS) who were indicated for surgery were enrolled and the informed consents were obtained. The angle of trunk rotation (ATR) was measured by the scoliometer. Apical vertebral rotation (AVR) was measured with EOS Imaging and CT images. Paired T tests were used to compare the measurements between ATR or AVR-EOS and AVR-CT. Pearson correlation analysis was performed to explore the relationship between ATR or AVR-EOS and AVR-CT. Then subgroup analysis was performed., Results: Forty-seven consecutive AIS patients with 62 curves were identified. In the whole group, the ATR, as well as AVR-EOS, was significantly smaller than the AVR-CT. Both ATR and AVR-EOS correlated with AVR-CT, although AVR-EOS correlated better. In thoracic group, there was no significant difference between ATR and AVR-CT ( P = .236). A significant correlation was found between ATR and AVR-CT(r = .574, P < .001). In TL/L group, no significant difference was noted between AVR-EOS and AVR-CT ( P = .414), and a significant correlation was found between AVR-EOS and AVR-CT(r = .824, P < .001)., Conclusion: ATR by scoliometer is numerically similar to AVR by CT and may evaluate the spinal rotation more appropriately in thoracic spine. AVR by EOS is numerically similar to AVR by CT and may be more applicable in TL/L spine. Appropriate methods could be selected according to the location of the curve., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Few studies have focused on the chronic spontaneous behavior of the unfused TL/L curve during follow-up. The purpose of the present study was to explore the behavior of the unfused TL/L curve during a long-term follow-up to identify the risk factors for correction loss., Methods: Sixty-four age-matched female AIS patients undergoing selective thoracic fusion were enrolled. Patients were divided into 2 groups according to whether there was correction loss. Risk factors for correction loss of the unfused TL/L curves were analyzed. The relationship and difference between the immediate postoperative thoracic and TL/L Cobb angles were explored., Results: The TL/L Cobb angle was 28.17° before surgery, 8.60° after surgery, and 10.74° at the final follow-up, with a correction loss of 2.14°. Each subgroup contained 32 cases. A smaller postoperative TL/L Cobb angle was the only risk factor that was independently associated with TL/L correction loss. In the LOSS group, there was a significant difference and no correlation between the immediate postoperative TL/L and the thoracic Cobb angle. In the NO-LOSS group, there was a moderate correlation and no difference between them., Conclusion: A smaller immediate postoperative TL/L Cobb angle may have been associated with TL/L correction loss during the long-term follow-up. Thus, good immediate postoperative spontaneous correction may not mean a satisfactory outcome at the final follow-up after STF. Mismatch between thoracic and TL/L Cobb angles immediately after surgery may also be related to correction loss of the unfused TL/L curves. Close attention should be paid in case of deterioration., (© 2023. The Author(s).)

Objectives: To compare the clinical and radiographic outcomes of oblique lateral lumbar interbody fusion and minimally invasive transforaminal lumbar interbody fusion in patients with grade-1 L4/5 degenerative spondylolisthesis., Methods: Based on the inclusion and exclusion criteria, the comparative analysis included consecutive patients with grade-1 degenerative spondylolisthesis who underwent oblique LIF (OLIF, n = 36) or minimally invasive transforaminal LIF (MI-TLIF, n = 45) at the Department of Spine Surgery, Beijing Jishuitan Hospital from January 2016 to August 2017. Patient satisfaction Japanese Orthopaedic Association score, visual analog scale (VAS) scores for back and leg pain, Oswestry disability index (ODI), radiographic outcomes including anterior/posterior disc heights (ADH/PDH), foraminal height (FH), foraminal width (FW), cage subsidence, cage retropulsion, and fusion rate were assessed during a 2-year follow-up. Continuous data are presented as mean ± standard deviation and were compared between groups using the independent sample t-test. Categorical data are presented as n (%) and were compared between groups using the Pearson chi-squared test or Fisher's exact test. Repetitive measurement and analysis of variance was employed in the analysis of ODI, back pain VAS score, and leg pain VAS score. Statistical significance was defined as p < 0.05., Results: The OLIF and MI-TLIF groups comprised 36 patients (age, 52.1 ± 7.2 years; 27 women) and 45 patients (age, 48.4 ± 14.4 years; 24 women), respectively. Satisfaction rates at 2 years post procedure exceeded 90% in both groups. The OLIF group had less intraoperative blood loss (140 ± 36 vs 233 ± 62 mL), lower back pain VAS score (2.42 ± 0.81 vs 3.38 ± 0.47), and ODI score (20.47 ± 2.53 vs 27.31 ± 3.71) at 3 months follow-up (with trends toward lower values at 2 years follow-up), but higher leg pain VAS scores at all postoperative time points than the MI-TLIF group (all p < 0.001). ADH, PDH, FD, and FW improved in both groups post-surgery. At the 2 year follow-up, the OLIF group had a higher rate of Bridwell grade-I fusion (100% vs 88.9%, p = 0.046) and lower incidences of cage subsidence (8.33% vs 46.67%, p < 0.001) and retropulsion (0% vs 6.67%, p = 0.046) than the MI-TLIF group., Conclusions: In patients with grade-I spondylolisthesis, OLIF was associated with lower blood loss and greater improvements in VAS for back pain and ODI and radiologic outcomes than MI-TLIF. The OLIF is more suitable for these patients with low back pain as the main symptoms are accompanied by mild or no leg symptoms before operation., (© 2023 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Introduction: Intervertebral disc degeneration (IVDD) is an important contributor of low back pain, which represents one of the most disabling symptoms within the adult population. Recently, increasing evidence suggests the potential association between Type 2 diabetes mellitus (T2DM) and IVDD. However, the causal relationship between these two common diseases remains unclear., Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal association between T2DM and IVDD. Sensitivity analysis was performed to test for heterogeneity and horizontal pleiotropy. Multivariable MR was also conducted to adjust for the effect of BMI on IVDD., Results: A total of 128 independent single-nucleotide polymorphisms (SNPs) that were significantly associated with T2DM were selected as instrumental variables in univariable MR analysis. Our results showed that patients with T2DM had a higher risk of developing IVDD (OR, 1.069; 95% CI, 1.026-1.115; p = 0.002). The relationship remained stable in sensitive analysis including multivariable MR, which implicated the direct causal effect of T2DM on IVDD (OR, 1.080; 95% CI, 1.041-1.121; p < 0.001) after adjusting for BMI., Conclusions: MR analysis indicated a causal effect of T2DM on IVDD, and the effect persisted even when we accounted for the impact of BMI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jin, Xing, Xiao, Wei, Yan, Zhao and Tian.)

Background: Ankylosing spondylitis (AS) is a chronic disorder characterized by an imbalance between bone formation and resorption. Spinal fractures often occur after minor trauma in patients with AS. For thoracolumbar fractures, transpedicular screw (TPS) fixation through the posterior approach has been suggested. The cortical bone trajectory (CBT) technique has also been used to prevent screw pull-out in patients with poor bone quality. The aim of current study was to assess the biomechanical characteristics of the TPS and CBT technique in thoracolumbar AS fracture fixation by finite element analysis. Methods: The three-dimensional finite element models of the AS spine were created. The CBT and TPS methods of screw insertion were used in AS spinal fracture models. An intact AS spine model was considered the control. An axial force and torsion in rotation, flexion/extension and lateral flexion were applied in all models in CBT, TPS, and control groups. Results: The AS spine showed similar construct stiffness after posterior fixation by CBT and TPS techniques under axial, rotational, and flexion/extension loading conditions. The TPS technique showed better intact stability under all loading conditions. Similarly, the TPS technique provided superior fracture regional stability against axial and rotational loads than did the CBT technique. The maximum von Mises stresses were 1714.4 ± 129.8 MPa and 1208.7 ± 107.3 MPa ( p < 0.001), which occurred in the CBT and TPS groups under compressive loading. Conclusions: The TPS technique provides better biomechanical strength under axial, rotational, flexion/extension, and lateral flexion loading than does the CBT technique. Compared with CBT, TPS is more effective in maintaining the stability of AS thoracolumbar fractures from a finite element analysis perspective., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tong, Xiao, Yan, Xing and Zhang.)

Background: To compare standalone oblique lateral interbody fusion (OLIF) vs. OLIF combined with posterior bilateral percutaneous pedicle screw fixation (OLIF combined) for the treatment of lumbar spondylolisthesis., Methods: This was a retrospective study of patients who underwent standalone OLIF or combined OLIF between 07/2014 and 08/2017 at two hospitals in China. Direct decompressions were not performed. Visual analog scale (VAS), Oswestry Disability Index (ODI), satisfaction rate, anterior/posterior disc heights (DH), foraminal height (FH), foraminal width (FW), cage subsidence, cage retropulsion, fusion rate, and complications were analyzed. All imaging examinations were read independently by two physicians and the mean measurements were used for analysis., Results: A total of 73 patients were included: 32 with standalone OLIF and 41 with combined OLIF. The total complication rate was 25.0% with standalone OLIF and 26.8% with combined OLIF. There were no differences in VAS and ODI scores by 2 years of follow-up, but the scores were better with standalone OLIF at 1 week and 3 months (P < 0.05). PDH and FW was smaller in the combined OLIF group compared with the standalone OLIF group before and after surgery (all P < 0.05). There were significant differences in FH before surgery and at 1 week and 3 months between the two groups (all P < 0.05), but the difference disappeared by 2 years (P = 0.111). Cage subsidence occurred in 7.3% (3/41) and 7.3% (3/41) of the patients at 3 and 24 months, respectively, in the combined OLIF group, compared with 6.3% (2/32) and 15.6% (5/32), respectively, in the standalone OLIF group at the same time points (P = 0.287). There was no cage retropulsion in both groups at 2 years. The fusion rate was 85.4%(35/41) in the combined OLIF group and 84.4% (27/32) in the standalone OLIF group at 3 months(P = 0.669). At 24 months, the fusion rate was 100.0% in the combined OLIF group and 93.8% (30/32) in the standalone OLIF group (P = 0.066)., Conclusion: Standalone OLIF may achieve equivalent clinical and radiological outcomes than OLIF combined with fixation for spondylolisthesis. The rate of complications was similar between the two groups. Patients who are osteoporotic might be better undergoing combined rather than standalone OLIF. The possibilty of proof lies within a future prospective study, preferably an RCT.

Background: There is no available literature for comparison on muscle atrophy between the "stand-alone" oblique lateral interbody fusion (OLIF) and regular OLIF (i.e., combined with percutaneous pedicle screws fixation (PPSF) in patients with spondylolisthesis). This study aimed to identify changes in back muscle atrophy between the two surgeries., Methods: This was a retrospective cohort study of patients who underwent OLIF or OLIF+PPSF at Beijing Jishuitan Hospital and Shanghai ChangZheng Hospital between 07/2014 and 10/2017. Computed tomography (CT) was used to measure functional cross-sectional area (FCSA) and fat infiltration percentage (FIP) of the multifidus and erector spinae before and 24 months after surgery., Result: There were no differences in FCSA and FIP between OLIF (n = 32) and OLIF+PPSF (n = 41) groups before surgery. In the OLIF group, the multifidus and erector spinae FCSA and FIP did not change at 24 months (FCSA: multifidus: from 8.59 ± 1.76 to 9.39 ± 1.74 cm 2 , P = 0.072; erector spinae: from 13.32 ± 1.59 to 13.55 ± 1.31 cm 2 , P = 0.533) (FIP: multifidus: from 15.91 ± 5.30% to 14.38 ± 3.21%, P = 0.721; erector spinae: from 11.63 ± 3.05% to 11.22 ± 3.12%, P = 0.578). In the OLIF+PPSF group, the multifidus and erector spinae FCSA decreased (multifidus: from 7.72 ± 2.69 to 5.67 ± 1.71 cm 2 , P < 0.001; erector spinae: from 12.60 ± 2.04 to 10.15 ± 1.82 cm 2 , P < 0.001), while the FIP increased (multifidus: from 16.13 ± 7.01% to 49.38 ± 20.54%, P < 0.001; erector spinae: from 11.93 ± 3.22% to 22.60 ± 4.99%, P < 0.001). The differences of FCSA and FIP between the two groups at 24 months were significant (all P < 0.001). The patients in the standalone OLIF group had better VAS back pain, and JOA scores than the patients in the OLIF combined group (all P < 0.05) at 1 week and 3 months after surgery. There were two cases (4.9%) of adjacent segment degeneration in the OLIF combined group, while there was no case in the OLIF alone group., Conclusions: Standalone OLIF had better clinical outcomes at 1 week and 3 months than OLIF+PPSF in patients with spondylolisthesis. OLIF may not result in paraspinal muscle atrophy at 24 months after surgery.

Study Design: Rat nucleus pulposus (NP) cells or annulus fibrosus (AF) cells were stimulated with conditioned media of RAW 264.7 macrophages and vice versa under healthy culture conditions and in the presence of pro-inflammatory mediators. The gene expression of pro-inflammatory mediators, extracellular matrix (ECM)-modifying enzymes, and chemokines, which play important roles in intervertebral disc degeneration (IDD), was determined., Objective: To test whether the interaction between native disc cells and infiltrating macrophages accelerates inflammation state, disrupts matrix homeostasis, and promotes inflammatory cells infiltration., Summary of Background Data: With macrophages infiltration, the disc resident cells would be inevitably exposed to macrophages. Macrophages have been shown to play pro-inflammatory role in the cellular interactions with disc cells under healthy culture conditions. However, the biologic interactions between macrophages and disc cells under degenerated disc inflammatory environment remain unknown., Methods: Murine Macrophages RAW 264.7 were cultured in the conditioned media of Rat AF or NP cells culture in the presence or absence of IL-1β stimulation. Similarly, Rat AF or NP cells were also cultured in the conditioned media of Murine Macrophages RAW 264.7 culture in the presence or absence of IFN-γ stimulation. The mRNA levels difference of pro-inflammatory genes, catabolic genes and chemokines genes for AF cells, NP cells and Macrophages RAW 264.7 were analyzed by qRT-PCR, respectively., Results: Compared with serum-free media exposure, RAW 264.7 macrophages exposed to AF or NP cells conditioned media selectively modestly upregulated mRNA levels of the aforementioned cytokines. Exposure of RAW 264.7 macrophages to conditioned media from AF or NP cells with IL-1β stimulation dramatically increased mRNA levels of all the investigated cytokines. Similarly, compared with serum-free media exposure, AF or NP cells exposed to RAW 264.7 macrophages conditioned media selectively modestly upregulated mRNA levels of the aforementioned cytokines. Exposure of AF or NP cells to conditioned media from RAW 264.7 macrophages with IFN-γ stimulation dramatically increased mRNA levels of all the investigated cytokines., Conclusion: The biologic interactions between infiltrating macrophages and native disc cells under degenerated disc inflammatory environment lead to an increasingly severe inflammatory conditions, which may be a self-stimulated process from the macrophages infiltration occurrenceLevel of Evidence: 5.

Objective: To analyze the causes of back pain after vertebroplasty or kyphoplasty., Methods: 1 863 patients with back pain who underwent vertebroplasty or kyphoplasty from Jan. 2004 to Dec. 2014 in Department of Spine Surgery, Beijing Jishuitan Hospital, were followed up for least 3 months after surgery with their back pain evaluated by VAS scores. Related information including preoperative, operative and postoperative factors was gathered. The VAS at last follow-up over 5 or the symptom relief less than 50% was considered as non-relieved, the correlations between the symptom relief and potential influencing factors were analyzed by the Spearman correlation., Results: Symptom relief was only correlated with postoperative complications (P<0.001). The back pain in 283 cases (15.2%) had not been relieved. Among them, 87 cases got fractures in other vertebrae (adjacent vertebrae in 67 cases, non-adjacent vertebrae in 20 cases); 3 cases got nonunion in the operated vertebrae; 1 case got postoperative infection; 6 cases got misdiagnosis and the other 186 cases had no known causes for the unrelieved pain., Conclusions: Postoperative back pain after vertebroplasty or kyphoplasty may have variable causes, and some of which have not been entirely understood. If the symptoms are not alleviated or even aggravate after active symptomatic treatment and anti-osteoporotic therapy, underlying causes such as re-fracture, nonunion, infection, pathologic fracture should be sought out.

Bone regeneration involves a series of events in a coordinated manner, including recruitment of mesenchymal stem cells, induction of immune response, inflammatory activity and vascular ingrowth. The microenvironment of bone regeneration is hypoxic. Low oxygen tension (hypoxia) promotes the upregulation of several signaling molecules. The primary mediating factor is the hypoxia-inducible factor-1 (HIF-1). Hypoxia stimulates the expression of a variety of cytokines from inflammatory cells, fibroblasts, endothelial cells, and osteoblasts. TNF-α is a key proinflammatory cytokine. The molecular events involved in osteoblast dysfunction under hypoxia are not fully understood. This study determined the effects of hypoxia on TNF-α in osteoblasts, and molecular mechanisms were explored. We observed that hypoxia induced TNF-α expression in a time-dependent manner in osteoblasts. Experiments using a potent HIF-1α activator DFO demonstrated that hypoxia-induced TNF-α was mediated by HIF-1-α. In addition, this study showed that hypoxia activated cyclooxygenase-2 (COX2) expression along with TNF-α. Inhibition experiments using COX2 inhibitor N398 indicated that COX2 was involved in hypoxia-mediated TNF-α expression, and this observation was further confirmed by Small interfering RNA against COX2. On the other hand, TNF-α didn't lead to the activation of COX2 expression. We conclude that COX2 is involved in hypoxia-induced TNF-α expression in osteoblast.

Purpose: To evaluate the safety and efficacy of three-dimensional (3D) navigation-guided polymethylmethacrylate (PMMA)-augmented thoracic and lumbar pedicle screw fixation for the osteoporotic patients., Methods: 27 consecutive osteoporosis patients with a variety of spinal disorders who underwent 3D navigation-guided PMMA-augmented pedicle screw fixation were evaluated clinically and radiologically in the perioperative and 1-year follow-up period. The improvement of Japanese Orthopaedic Association (JOA) scores was analyzed. PMMA leakage and other complications were inspected intraoperatively and postoperatively. Screw loosening and bone fusion were evaluated radiographically during follow-up., Results: 8 patients had thoracic and lumbar fractures; 18 patients had degenerative spinal disorders; one patient had revision surgery. One patient died of postoperative pneumonia. Each of the other 26 patients was followed up regularly at 3, 6, 12 and 18 months postoperatively. The mean therapeutic improvement rate is 39.6% evaluated by JOA scores. 2 patients (7.4%) had leakage into the spinal canal in front of the posterior longitudinal ligament and two patients (7.4%) had leakage into the prevertebral soft tissue inspected by the postoperative CT scans. No pedicle cortex breach and cement leakage surrounding pedicle cortex were observed. None of patients complained of dyspnoea and showed evidence of pulmonary embolism. Bone fusions were found in 20 patients (bony fusion rate 76.9%) at the 12-month follow-up and no screw loosening occurs., Conclusion: The results show favorable outcome using 3D navigation-guided PMMA-augmented thoracic and lumbar pedicle screw fixation for the osteoporosis patients both clinically and radiologically.

Background: Lateral pedicle wall perforations occur frequently during pedicle screw insertion. Although it is known that such an occurrence decreases the screw pull-out strength, the effect has not been quantified biomechanically., Materials and Methods: Twenty fresh cadaveric lumbar vertebrae were harvested, and the bone mineral density (BMD) of each was evaluated with dual-energy radiography absorptiometry (DEXA). Twenty matched, 6.5-mm pedicle screws were inserted in two different manners in two groups, the control group and the experimental group. In the control group, the pedicle screw was inserted in a standard fashion taking adequate precaution to ensure there was no perforation of the wall. In the experimental group, the pedicle screw was inserted such that its trajectory perforated the lateral wall. Group assignments were done randomly, and the maximal fixation strength was recorded for each screw pull-out test with a material-testing system (MTS 858 II)., Results: The average BMD for both groups was 0.850 g/cm(2) (0.788-0.912 g/cm(2)). The average (and standard deviation) maximal pull-out forces were 1,015.8 ± 249.40 N for the experimental group and 1,326.0 ± 320.50 N for the control group. According to a paired t-test, the difference between the two groups was statistically significant (P < 0.001)., Conclusion: The results of this study confirm that the maximal pull-out strength of pedicle screws decreases by approximately 23.4% when the lateral wall is perforated.

The nature of the cellular and molecular mechanisms for the transition of avascular cartilage replacement with bone during endochondral ossification remains poorly understood. One of the driving forces is hypoxia. As a master regulator of hypoxia, hypoxia-inducible factor-1α (HIF-1α) has been reported to couple angiogenesis to osteogenesis. Our recent study has demonstrated that osteoblast growth is inhibited under hypoxia and that HIF-1α cooperates with Osterix (Osx) to inhibit Wnt pathway. However, molecular mechanisms for inhibitory effects of HIF-1α on Wnt pathway are not well understood. In this study, our quantitative RT-PCR results revealed that the expression of a Wnt antagonist Sclerostin (Sost) was upregulated in osteoblasts during hypoxia while HIF-1α was upregulated. Treatment of desferrioxamine (DFO), a HIF-1α activator, led to further increase of Sost expression, suggesting that HIF-1α may activate Sost expression. The regulation of Sost gene expression by HIF-1α was then investigated. We performed loss-of-function experiments to examine Sost expression by using siRNA approach against HIF-1α, and found that the inhibition of HIF-1α by siRNA in osteoblasts led to the decrease of Sost expression. To address transcriptional regulation of Sost gene by HIF-1α, transient transfection assay was performed and showed that HIF-1α activated Sost-1 kb promoter reporter activity in a dose-dependent manner. To narrow down the minimal region of Sost promoter activated by HIF-1α, we generated a series of deletion mutants of Sost constructs. It was demonstrated that Sost-260 was the minimal region of Sost promoter for HIF-1α activation and that Sost-106 construct, which lack hypoxia response element, abolished HIF-1α-mediated Sost reporter activation. Gel shift assay showed that HIF-1 bound to the promoter sequence of Sost directly. These findings support our hypothesis that HIF-1α activates Sost expression. This study provides a novel molecular mechanism through which HIF-1α inhibits Wnt signaling in osteoblasts.

Osterix (Osx) is an osteoblast-specific transcription factor required for osteoblast differentiation. Inhibition of Wnt pathway by Osx highlights the potential for feedback control mechanisms involved in bone formation. Hypoxia-inducible factor-1α (HIF-1α) is a master regulator of hypoxia. HIF-1α has been reported to couple angiogenesis to osteogenesis. Our recent study has demonstrated that Osx and HIF-1α cooperatively regulate VEGF expression in osteoblasts. Effects of hypoxia/HIF-1α on osteoblast proliferation and related mechanisms are not well understood. In this study, osteoblast growth under hypoxia was examined. We observed that osteoblast growth was inhibited under hypoxia. To explore possible mechanisms for hypoxia/HIF-1α to inhibit osteoblast proliferation, we tested the effect of hypoxia/HIF-1α on Wnt pathway. Quantitative RT-PCR results revealed that Wnt target genes such as cyclin D1 and c-Myc were downregulated under hypoxia while HIF-1α was upregulated. Treatment of desferrioxamine, a HIF-1α activator, led to further downregulation of expressions of cyclin D1 and c-Myc in osteoblasts. On the contrary, the inhibition of HIF-1α by siRNA in osteoblasts led to the expression increase of cyclin D1 and c-Myc. These data suggest that HIF-1α inhibits Wnt pathway in osteoblasts. To examine the effect of HIF-1α on Wnt pathway, HIF-1α was cotransfected with β-catenin along with Topflash reporter in transient transfection assay. Our results showed that HIF-1α inhibited β-catenin-induced Topflash reporter activity. Interestingly, a synergistic interplay was observed between Osx and HIF-1α in the inhibition of β-catenin-induced Topflash expression. Our findings indicate that Osx and HIF-1α cooperatively inhibit Wnt pathway. This study revealed additional new information of the cooperation between HIF-1α and Osx in osteoblasts.