Unilateral high-riding vertebral artery is associated with asymmetric morphological changes of the atlantoaxial joint: a novel risk factor for atlantoaxial osteoarthritis.

PURPOSE: This study aimed to investigate the association between unilateral high-riding vertebral artery (HRVA) and morphological changes in the atlantoaxial joint (AAJ) and to determine whether unilateral HRVA is a risk factor for atlantoaxial osteoarthritis (AAOA). METHODS: We conducted a retrospective analysis of 2496 patients admitted to our medical center between January 2020 and December 2022 who underwent CT imaging of the cervical spine. Two hundred and seventy-two patients with unilateral HRVA (HRVA group) were identified and a respective 2:1 age- and sex-matched control group without HRVA was built. Morphological parameters, including C2 lateral mass settlement (C2 LMS), C1/2 coronal inclination (C1/2 CI), lateral atlanto-dental interval (LADI), and C1/2 relative rotation angle (C1/2 RRA) were measured. The degree of AAOA was recorded. Risk factors associated with AAOA were identified using univariate and multivariable logistic regression analyses. RESULTS: The study included 61.4% women, and the overall average age of the study population was 48.7 years. The morphological parameters (C2 LMS, C1/2 CI, and LADI) in AAJ were asymmetric between the HRVA and the non-HRVA sides in the HRVA group (p < 0.001). These differences in parameters (d-C2 LMS, d-C1/2 CI, and d-LADI) between the HRVA and the non-HRVA sides, and C1/2 RRA were significantly larger than those in the control group. Eighty-three of 816 patients (10.2%) with AAOA had larger values of d-C2 LMS, d-C1/2 CI, d-LADI, and C1/2 RRA compared with the patients without AAOA (p < 0.05). The multivariable logistic regression analysis indicated that unilateral HRVA [adjusted odds ratio (OR) = 2.6, 95% CI: 1.1-6.3, p = 0.029], age in the sixth decade or older (adjusted OR = 30.2, 95% CI: 16.1-56.9, p < 0.001), women (adjusted OR = 2.1, 95% CI: 1.0-5.6, P = 0.034) were independent risk factors for AAOA. CONCLUSION: Unilateral HRVA was associated with asymmetric morphological changes of nonuniform settlement of C2 lateral mass, lateral slip of atlas, and atlantoaxial rotation displacement. Besides age ≥ 60 years and females, unilateral HRVA is an independent risk factor for AAOA.

Prevalence and Risk Factors for Cervical Adjacent Segment Disease and Analysis of the Clinical Effect of Revision Surgery: A Minimum of 5 Years' Follow-Up.

STUDY DESIGN: A retrospective study was performed. OBJECTIVE: To investigate the prevalence and risk factors for adjacent segment disease (ASD) after anterior cervical discectomy and fusion (ACDF) and the clinical efficacy of revision surgery. METHOD: A total of 219 patients treated with ACDF were analyzed retrospectively. Demographic characteristics, including age, sex, body mass index (BMI) and bone mineral density (BMD), and radiographic measurements, including C2-C7 cervical sagittal vertical axis (cSVA), T1 slope (T1S), thoracic inlet angle (TIA) and C2-C7 Cobb angle, were analyzed. Modified Japanese Orthopaedic Association (mJOA) score and visual analog scale (VAS) score were used to evaluate patient function. Parameters were analyzed with Student's t test, and potential risk factors for ASD were further analyzed with multivariate logistic regression analysis. RESULTS: The incidence of ASD after ACDF surgeries was 21%. The severity of osteoporosis, BMI and C2-C7 cSVA were significantly higher in the ASD group than in the NASD group (P < .05). The preoperative and postoperative TIAs were lower in the ASD group (P < .05). Multivariate logistic regression analysis showed that a high BMI, severe osteoporosis and a high C2-C7 cSVA were risk factors for ASD after ACDF (P < .05). The postoperative TIA and postoperative T1S were also correlated with ASD (P < .05). CONCLUSION: Patients with a high BMI, severe osteoporosis, and a large C2-C7 cSVA after ACDF have a higher risk of ASD, while a large T1S and TIA may be protective factors. In addition, revision surgery can restore cervical spine balance in patients with ASD and promote better clinical outcomes.

The association between unilateral high-riding vertebral artery and atlantoaxial joint morphology: a multi-slice spiral computed tomography study of 396 patients and a finite element analysis.

BACKGROUND CONTEXT: A high-riding vertebral artery (HRVA) can deviate too medially, too posteriorly, or too superiorly to allow the safe insertion of screws. However, it is unknown whether the presence of a HRVA is associated with morphological changes of the atlantoaxial joint. PURPOSE: To investigate the association between HRVA and atlantoaxial joint morphology in patients with and without HRVA. STUDY DESIGN: A retrospective case-control study and finite element (FE) analysis. PATIENT SAMPLE: A total of 396 patients with cervical spondylosis underwent multi-slice spiral computed tomography (MSCT) of cervical spine at our institutions from 2020 to 2022. OUTCOME MEASURES: A series of atlantoaxial joint morphological parameters, including C2 lateral mass settlement (C2 LMS), C1-2 sagittal joint inclination (C1-2 SI), C1-2 coronal joint inclination (C1-2 CI), atlanto-dental interval (ADI), lateral atlanto-dental interval (LADI), and C1-2 relative rotation angle (C1-2 RRA) were measured, and lateral atlantoaxial joints osteoarthritis (LAJs-OA) was recorded. The stress distribution on the C2 facet surface under different torques of flexion-extension, lateral bending, and axial rotation was analyzed by FE models. A 2-Nm moment was applied to all models to determine the range of motion (ROM). METHODS: A total of 132 consecutive cervical spondylosis patients with unilateral HRVA were enrolled in the HRVA group, and 264 patients without HRVA matched for age and sex were enrolled in the normal (NL) group. Atlantoaxial joint morphological parameters were compared between two sides of C2 lateral mass within HRVA or NL group, and between HRVA and NL groups. A 48-year-old woman with cervical spondylosis without HRVA was selected for cervical MSCT. A three-dimensional (3D) FE intact model of the normal upper cervical spine (C0-C2) was created. We established the HRVA model by simulating atlantoaxial morphological changes of unilateral HRVA with FE method. RESULTS: The C2 LMS was significantly smaller on the HRVA side than that on the non-HRVA side in the HRVA group, but C1-2 SI, C1-2 CI, and LADI on HRVA side were significantly larger than those on non-HRVA side. There was no significant difference between left and right sides in the NL group. The difference in C2 LMS (d-C2 LMS) between HRVA side and non-HRVA side in the HRVA group was larger than that in the NL group (P < 0.05). Meanwhile, the differences in C1-2 SI (d-C1/2 SI), C1-2 CI (d-C1/2 CI), and LADI (d-LADI) in the HRVA group were significantly larger than those in the NL group. The C1-2 RRA in the HRVA group was significantly larger than that in the NL group. Pearson correlations showed that d-C1/2 SI, d-C1/2 CI, and d-LADI were positively associated with d-C2 LMS (r=0.428, 0.649, 0.498, respectively, p<.05 for all). The incidence of LAJs-OA in the HRVA group (27.3%) was significantly larger than that in the NL group (11.7%). Compared with the normal model, the ROM of C1-2 segment declined in all postures of the HRVA FE model. We found a larger distribution of stress on the C2 lateral mass surface of the HRVA side under different moment conditions. CONCLUSIONS: We suggest that HRVA affects the integrity of the C2 lateral mass. This change in patients with unilateral HRVA is associated with the nonuniform settlement of the lateral mass and an increase in the lateral mass inclination, which may further affect the degeneration of the atlantoaxial joint because of the stress concentration on the C2 lateral mass surface.

Multisegment transforaminal lumbar interbody fusion (TLIF) combined with Ponte osteotomy in degenerative lumbar scoliosis (DLS) surgery: a minimum of five years' follow-up.

PURPOSE: To evaluate the long-term clinical outcomes of degenerative lumbar scoliosis (DLS) with the administration of multisegment transforaminal lumbar interbody fusion (TLIF) combined with Ponte osteotomy long-level fixation fusion, as well as to identify the factors affecting health-related quality of life (HRQOL). METHODS: This was a retrospective single-centre study involving comprehensive clinical data. The Oswestry Disability Index (ODI), visual analog scale (VAS) outcomes, and Scoliosis Research Society (SRS-22) questionnaire were recorded to assess HRQOL. A correlation analysis was performed to determine the association between HRQOL and radiographic parameters. RESULTS: A total of 41 consecutive patients (15 males and 26 females) met the inclusion criteria with a follow-up of 8.62 ± 1.20 years. Factors associated with HRQOL were significantly improved post-operation. Global sagittal parameters, including the sagittal vertebral axis (SVA) and T1 pelvic angle (TPA), and local parameters, including apical vertebral translation (AVT) and apical vertebral rotation (AVR), were significantly improved at the last follow-up. Significantly strong correlations between each clinical and radiographic parameter were demonstrated. Moreover, a multiple linear regression analysis demonstrated that the differences in AVT and AVR were significantly correlated with the difference in lumbar lordosis (LL), which was significantly correlated with the differences in SVA and TPA. CONCLUSION: The surgical treatment of DLS with multisegment TLIF accompanied by Ponte osteotomy and long-level fixations improved the quality of life of patients with a long-term effect. AVR correction is an important factor for LL restoration that significantly correlates with improvements in the sagittal balance parameters SVA and TPA, which are key factors for guaranteeing good HRQOL.

Up-regulation of TßRIII facilitates the osteogenesis of supraspinous ligament-derived fibroblasts from patients with ankylosing spondylitis.

Spinal supraspinous ligament (SL) osteogenesis is the key risk of ankylosing spondylitis (AS), with an unclear pathogenesis. We previously found that transforming growth factor ß1 (TGF-ß1), bone morphogenetic proteins (eg BMP2) and type III TGF-ß1 receptor (TßRIII) expression were markedly up-regulated in AS-SLs. However, the roles of these closely related molecules in AS are unknown. Here, we showed that BMP2, TGF-ß1, TßRIII and S100A4 (a fibroblast marker) were abundant in active osteogenic AS-SL tissues. In vitro, AS-SL fibroblasts (AS-SLFs) showed high BMP2, TGF-ß1 and TßRIII expression and auto-osteogenic capacity. We further evaluated the role of TßRIII in the osteogenesis of normal SLFs. BMP2 combined with TGF-ß1 induced the osteogenesis of TßRIII-overexpressing SLFs, but the activity was lost in SLFs upon TßRIII knockdown. Moreover, our data suggested that BMP2 combined with TGF-ß1 significantly activated both TGF-ß1/Smad signalling and BMP2/Smad/RUNX2 signalling to induce osteogenesis of SLFs with TßRIII up-regulation. Furthermore, our multi-strategy molecular interaction analysis approach indicated that TGF-ß1 presented BMP2 to TßRIII, sequentially facilitating BMP2 recognition by BMPR1A and promoting the osteogenesis of TßRIII-overexpressing SLFs. Collectively, our results indicate that TGF-ß1 combined with BMP2 may participate in the osteogenic differentiation of AS-SLF by acting on up-regulated TßRIII, resulting in excessive activation of both TGF-ß1/Smad and BMP2/BMPR1A/Smad/RUNX2 signalling.

Bacillus alkalicellulosilyticus sp. nov., isolated from extremely alkaline bauxite residue (red mud) site.

A Gram-stain-negative, rod-shaped, facultatively anaerobic, motile and spore-forming strain designated FJAT-44921T was isolated from red mud collected from Chiping County, Shandong Province, China. The 16S rRNA gene sequence result showed that strain FJAT-44921T shared a low sequence identity (96.6%) with the members of the genus Bacillus. Growth was observed at pH 8.0-10.0 (optimum pH 9.0), 10-40 °C (optimum 20-25 °C) with 0-8% (v/w %) NaCl (optimum 4-6 v/w %). FJAT-44921T consists of MK-7 as the isoprenoid quinone and meso-2,6-diaminopimelic acid as the cell-wall diamino acid. The predominant fatty acids were anteiso-C15:0, iso-C15:0, C16:0, and anteiso-C17:0. The polar lipids were diphosphatidylglycerol, phosphatidyl glycerol, phosphatidylmethylethanolamine, unidentified phospholipid, and unidentified aminophospholipid. The genomic DNA G + C content was 37.3 mol%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between FJAT-44921T and other closely related Bacillus members were lower than the recognized threshold values of ANI (95-96%) and dDDH (70%) recommended as the criterion for interspecies identity. The type strain is FJAT-44921T (=CCTCC AB 2016196T =DSM 104630T).

Preliminary investigation of bilateral internal iliac artery ligation and anterior tumor separation through laparoscopy before posterior resection of a giant sacral tumor.

BACKGROUND: Surgical is the optimal therapeutic strategy for sacral tumors, and complete resection can effectively improve the recurrence and survival rates. However, the specialized anatomy, massive bleeding and adhesion to the anterior tissue, especially that caused by giant sacral tumors, makes complete resection difficult. The laparoscopic technique provides a new method to resect sacral tumors. METHODS: 34 patients with primary giant sacral tumors who underwent surgical resection were enrolled. After bilateral internal iliac artery ligation and anterior laparoscopic tumor separation, the sacral tumors were successfully resected posteriorly. The clinical, radiological and follow-up data were collected and analyzed. RESULTS: The average operative time was 276.47 min and that for laparoscopy was 76.24 min. The average intraoperative blood loss was 1757.64 ml. No complications associated with laparoscopic surgery, such as intestinal, urinary tract, or vascular injuries, occurred. Ten patients (29.41%) had perioperative complications, including infection, unhealed wounds, and cerebrospinal fluid leaks in 10, 5 and 2 patients, respectively. Patients with complications had significantly longer total (55.00 ± 34.53 vs 25.13 ± 14.60, P = 0.001) and postoperative (39.10 ± 30.61 vs 14.83 ± 10.00, P = 0.002) hospitalization stays than patients without complications. Postoperatively, bowel and bladder dysfunction, intestinal obstruction, pain, and perianal numbness occurred in 21, 5, 8, and 2 patients, respectively. The recurrence rate was 11.76%. CONCLUSIONS: Laparoscopically assisted sacral tumor resection is a technically feasible and effective surgical method to resect giant sacral tumors, with the advantages of reduced operative blood loss during internal iliac artery ligation and anterior tumor separation.

Tissue-engineered bone used in a rabbit model of lumbar intertransverse process fusion: A comparison of osteogenic capacity between two different stem cells.

Spinal fusion serves an important role in the reconstruction of spinal stability via restoration of the normal spinal sequence and relief of pain. Studies have demonstrated that the fusion rate is mainly associated with the osteogenic capacity of the implanted graft. Mesenchymal stem cells (MSCs) have been successfully isolated from human degenerated cartilage endplate (CEP) and designated as CEP-derived stem cells (CESCs). Previous studies have suggested that CESCs possesses in vitro and in vivo chondrogenic potential superior to that of bone marrow (BM)-MSCs. In addition, CESCs have shown a stronger in vitro osteogenic ability. The present study aimed to further determine the in vivo three-dimensional osteogenesis efficacy of CESCs for spinal fusion. Tissue-engineered bone grafts were transplanted into a rabbit model of posterolateral lumbar intertransverse process fusion using CESCs and BM-MSCs as seed cells composited with porous hydroxyapatite (PHA). The results of manual palpation and computed tomography (CT) scan reconstruction indicated that the CESCs/PHA group had a higher fusion rate than the BM-MSCs/PHA group, although the difference was not observed to be statistically significant. In addition, RT-qPCR results revealed that the in vitro CESCs/PHA composite expressed significantly higher levels of osteogenic-specific mRNA compared with the BM-MSCs/PHA composite. Finally, micro-CT and semi-quantitative histological analysis further demonstrated that the newly formed bone quality of the CESCs/PHA group was significantly higher than that of the BM-MSCs/PHA group in the intertransverse process fusion model. Therefore, the study indicated that CESCs possess superior in vivo osteogenesis capacity compared with BM-MSCs, and might serve as an important alternative seed cell source for bone tissue engineering. These results may provide the foundation for a biological solution to spinal fusion or other bone defect issues.

Single-stage posterior total en bloc spondylectomy in the treatment of lumbar spinal metastases.

OBJECTIVE: To report the clinical and radiographic outcomes of single-stage posterior total en bloc spondylectomy (TES) of lumbar spinal metastases. PATIENTS AND METHODS: From January 2012 to January 2015, 20 consecutive cases with lumbar spinal metastases who received single-stage posterior TES were retrospectively analyzed. A visual analog scale (VAS) was used to evaluate patients' pain status, American Spinal Injury Association (ASIA) classification was used to evaluate neurological status, and Eastern Cooperative Oncology Group (ECOG) score system was used to evaluate patients' performance status at pre- and post-operation and final follow-up. In addition, Intraoperative blood loss, operative time, postoperative complications, local kyphosis angle, and the postoperative duration of hospital stay were analyzed. RESULTS: The median follow-up time was 16 months (ranging from 3 to 39 months), and 4 patients were still alive at the last follow-up. The mean amount of intraoperative blood loss and operation time was 970 mL and 232.5 min, respectively. The average VAS score improved from 7.5 preoperative to 2.8 postoperative and 3.2 at the last follow-up. Postoperative complications occurred in 3 cases. Sixteen patients died within 2 years after surgery, 10 of which died within 1 year. In the remaining 4 patients, the mean follow-up period was 37.25 months. One case of local recurrence occurred but no implant failure presented during follow-up. CONCLUSIONS: Single-stage posterior TES is a challenging but rewarding procedure in the treatment of lumbar spinal metastases. Due to unique anatomy and biomechanics, surgeons should be aware of important vessels, and nerve root injury should be avoided.

Sema4D expression and secretion are increased by HIF-1α and inhibit osteogenesis in bone metastases of lung cancer.

Most lung cancer bone metastasis are characterized by osteolytic destruction and osteoblastic activity is significantly decreased, suggesting that hypoxia may play a critical role in the process, but the underlying mechanisms remain unknown. Semaphorin 4D (Sema4D) is a recently discovered osteogenic inhibitory factor that is expressed at high levels in lung cancers. Here, CoCl2-induced hypoxia significantly enhanced the inhibitory effect of lung cancer cell conditioned media on osteoblast differentiation by inducing the expression and secretion of Sema4D in a HIF-1α- but not HIF-2α-dependent manner. Moreover, HIF-1α directly regulated Sema4D expression by binding to bases 1171 to 798 in the Sema4D promoter. Furthermore, hypoxia increased Sema4D secretion by upregulating a disintegrin and metalloproteinase 17 (ADAM17) expression in lung cancer in a HIF-1α-dependent manner. In bone metastasis samples from 49 patients with lung cancer, Sema4D and ADAM17 expression significantly correlated with HIF-1α expression and strongly correlated with a poor differentiation status and osteolytic bone destruction. These results provide the first evidence that HIF-1α-induced Sema4D expression and secretion play important roles in lung cancer osteolytic bone metastasis by inhibiting osteoblast differentiation, thereby providing potential strategies for the treatment of bone metastasis via targeting osteoblasts.

Prognostic Factors and Comparison of Conservative Treatment, Percutaneous Vertebroplasty, and Open Surgery in the Treatment of Spinal Metastases from Lung Cancer.

BACKGROUND: Spinal metastases from lung cancer could result in life-threatening consequences. Few studies report the prognostic factors and compare different treatments in patients with spinal metastases from lung cancer. METHODS: From 2005 to 2014, we retrospectively reviewed and studied 140 patients with spinal metastases from lung cancer according to different treatments. To estimate overall survival and identify prognostic factors for survival, the Kaplan-Meier method and Cox regression analysis were adopted. In addition, the Kaplan-Meier method was used to compare different treatments for overall survival. RESULTS: All patients in a conservative group and a percutaneous vertebroplasty group died at a median survival time of 7 months for both groups. As for patients in the open-surgery group, 42 patients died at a median of 11 months, and 7 patients who were still alive at the time of this study were followed for a median of 29 months. Multivariate analysis suggested that better survival was significantly associated with American Spinal Injury Association grade D/E on admission, American Spinal Injury Association grade E after surgery, Eastern Cooperative Oncology Group performance status 1-2, and adjuvant radiation therapy in all 3 groups. In addition, Kaplan-Meier analysis showed that the overall survival rate of the open-surgery group (14.3%) was better than that of conservative group (0%) and the percutaneous vertebroplasty group (0%). CONCLUSIONS: A better overall survival outcome might be achieved by a series of comprehensive and individualized treatments and personalized treatment.

Anterior reduction and fusion for treatment of massive tear drop fracture of axis combining with inferior endplate serious traversed lesion: A retrospective study.

BACKGROUND: Tear drop fracture of axis represents a very small percentage of injuries of the cervical spine, but there is controversy about the treatment method for tear drop fracture of axis, especially when a large avulsed fragment is significant displacement, which combined with the inferior endplate serious traversed lesion of axis. OBJECTIVE: To evaluate the clinical outcome of anterior reduction, graft fusion of C2-3 and plate fixation in the management of massive tear drop fracture of axis combining with inferior endplate serious traversed lesion of axis. METHODS: There were 7 patients with a massive tear drop fracture of axis combining with inferior endplate serious traversed lesion. The avulsed ratio of inferior endplate of axis was 46.8 ± 13.4%, the average angle of rotation of the avulsed fragment was 30.4 ± 11.7, and the average displacement was 7.7 ± 2.8 mm. The posterior displacement of axis body was observed with three patients. All patients underwent anterior reduction, graft fusion of C2-3 and plate fixation with high anterior cervical retropharyngeal approach. The follow-up ranges from 2 years to 5 years. RESULTS: In all cases, tear drop fracture was reduced completely, avulsed fragment got bony healing, and bone graft achieved bony fusion at C2-3. There were no local angle deformity and rotated deformity in all patients, and there were normal physiological lordosis and good stabilization of upper cervical spine. The neurological function of one patient with American Spine Injury Association (ASIA) impairment scale type D was improved to type E postoperatively. Six patients without neurological lesion had no neurological syndrome after operation. CONCLUSIONS: Anterior surgical procedures would be an effective treatment of massive tear drop fracture of axis combining with inferior endplate serious traversed lesion. Complete reduction, sufficient stabilization and normal physiological lordosis of upper cervical spine could be achieved postoperatively.

Distinguishing characteristics of stem cells derived from different anatomical regions of human degenerated intervertebral discs.

INTRODUCTION: Several types of stem cells have been successfully demonstrated to exist in the human degenerated intervertebral disc (IVD), which is composed of annulus fibrosus (AF), nucleus pulposus (NP) and cartilage endplate (CEP). However, the differences in the biological characteristics among these and bone marrow derived mesenchymal stem cells (BM-MSCs) remain unclear. MATERIALS AND METHODS: To investigate this issue, cells were harvested from human AF, NP, CEP, and bone marrow, respectively; passage 2 cells were selected using the agarose suspension culture system to obtain stem cell clones. Following expansion in vitro, stem cells from different anatomical regions were compared regarding the morphology, proliferation ability, immunophenotypic expression, and multi-lineage differentiation capacity. In addition, stem cell-alginate bead compositions were constructed for the comparison of DNA and sGAG content. RESULTS: There were subtle differences regarding cell morphology, but no significant differences in proliferation ability among the four types of stem cells. For the immunophenotypic analysis, all stem cells basically fulfilled the criteria for mesenchymal stem cells (MSCs), which have been published by the International Society for Cellular Therapy (ISCT), with a significant difference in CD105 expression. A comparison of the osteogenic capacities indicated: cartilage endplate-derived stem cells (CESCs) > annulus fibrosus-derived stem cells (AFSCs) > BM-MSCs > nucleus pulposus-derived stem cells (NPSCs). The chondrogenesis difference was similar to osteogenesis. For adipogenesis: BM-MSCs >NPSCs >CESCs >AFSCs. In the stem cell/alginate composition, the CESCs consistently showed the superior chondrogenic potential among all those cell types. CONCLUSIONS: Our data indicated that all the four types of stem cells shared some similar biological properties (regarding shape, proliferation ability and immunophenotypic expression). CESCs, which had the strongest osteogenic and chondrogenic potentials, may serve as excellent seed cells for NP/cartilage or bone tissue engineering.

Breast cancer cells promote osteoblastic differentiation via Sema 3A signaling pathway in vitro.

Breast cancer bone metastases are attributed to multiple cellular and molecular interactions between the cancer cells and the bone microenvironment. Some breast cancers (about 10%) manifest predominant osteoblastic bone metastases. However, the effects of cancer cell-produced factors on osteoblastic differentiation are not fully understood. Semaphorin 3A (Sema 3A) is a newly identified regulatory factor of bone rebuilding. In the present study, we demonstrated that human breast cancer MCF-7 cells, which preferentially form osteoblastic bone metastases, exhibited increased Sema 3A expression levels. We also found that MCF-7 cell-derived Sema 3A stimulated osteoblastic differentiation and nuclear ß-catenin accumulation, and these effects could be blocked by shRNA Sema 3A or a Sema 3A-neutralizing antibody. In conclusion, our data suggest that MCF-7 cell-derived Sema 3A plays a causative role in osteoblastic bone metastases progression by stimulating osteoblastic differentiation.

Suppression subtractive hybridization reveals differentially expressed genes in supraspinous ligaments of patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a severe chronic inflammatory disease that may ultimately result in the development of a 'bamboo­like' spine. Although the pathological changes that occur in AS have been extensively investigated, the mechanism underlying spinal fusion during AS remains elusive. Differentially expressed genes (DEGs) in paraspinal tissues from patients with AS compared with those from healthy controls were therefore investigated. Polymerase chain reaction (PCR)­based suppression subtractive hybridization was performed using total mRNA from the supraspinal ligaments of three patients with AS and three patients with spinal fractures as controls. From this, 27 genes were identified in all of the three independent forward libraries, which were defined as DEGs associated with AS. Reverse transcription­quantitative PCR demonstrated that six DEGs were overexpressed in the tissues from patients with AS compared with those from individuals in the control group, including those encoding transforming growth factor ß types I and III receptor, vascular endothelial growth factor, matrix metalloproteinase­3, core­binding factor α1 and bone morphogenetic protein 2. Western blot analysis showed increased expression in all six of these proteins in the samples from patients with AS compared with those in the control groups. These findings suggested that changes in the expression of these genes and proteins are associated with the development of spinal fusion during the pathogenesis of AS. Furthermore, these genes may be novel markers of the risk of developing AS, in addition to being targets for the treatment of this disease.

Single-nucleotide polymorphisms of the PRKCG gene and osteosarcoma susceptibility.

The objective of this study was to explore the relationship between single-nucleotide polymorphisms (SNPs) of the protein kinase C gamma (PRKCG) gene and osteosarcoma susceptibility in Chinese Han population. A total of 610 cases of osteosarcoma patients and 610 healthy individuals were enrolled in this study. TaqMan method was used to compare genotypes and the allelic distribution frequency of three SNPs (rs454006, rs2242245, and rs8103851) in the PRKGG gene between osteosarcoma patients and healthy individuals. Osteosarcoma patients were grouped according to different clinical parameters (age, gender, pathological types, tumor location, Enneking staging, tumor metastasis and treatment) to compare genotype and allele frequency among different groups as well as to explore the relationship between gene polymorphisms and different clinical parameters. The rs454006 polymorphisms of the PRKCG gene include the CC, CT, and TT genotypes. The differences in genotype frequency and allele frequency between osteosarcoma patients and healthy individuals were significant (both P < 0.001). There was no significant different between osteosarcoma patients and healthy individuals in rs8103851 and rs2242245 polymorphisms of the PRKCG gene (both P > 0.05). The differences of the rs8103851 genotype frequency and allele frequency in patients with metastatic osteosarcoma and patients without metastasis were significant (both P < 0.001). The distribution frequencies of the CG and GG genotypes as well as the G allele in patients with metastatic osteosarcoma were higher than in patients without metastasis. The genotype frequency and allele frequency of rs454006 and rs2242245 did not correlate with clinical parameters. The rs454006 polymorphism of the PRKCG gene correlated to osteosarcoma susceptibility and might increase the risk of osteosarcoma. The rs8103851 correlated to metastatic osteosarcoma and could be risk factors for metastatic osteosarcoma.

Utilization of stem cells in alginate for nucleus pulposus tissue engineering.

In a general view of anatomy, intervertebral disc is composed of three parts: annulus fibrosus (AF), nucleus pulposus (NP), and cartilage endplate (CEP). Recently, several types of stem cells were successfully isolated from these corresponding regions, but up to now, no research was performed about which kind of stem cells is the most efficient candidate for NP tissue engineering or for stem cell-based disc regeneration therapy. In this study, we compared the regenerative potentials of the above-mentioned three kinds of disc-derived stem cells with that of the classic bone marrow (BM)-mesenchymal stem cells (MSCs) in a rabbit disc degeneration model. By magnetic resonance imaging (MRI), X-ray, histology, etc. evaluations, we found that cartilage endplate-derived stem cells (CESCs) showed superior capacity compared with the annulus fibrosus-derived stem cells (AFSCs), nucleus pulposus-derived stem cells (NPSCs), and BM-MSCs (p<0.05); additionally, when comparing the CESC group with the normal control group, there existed no statistical difference in X-ray (p>0.05). Those results demonstrated that the CESC-seeded alginate construct performed the most powerful ability for NP regeneration, while AFSCs showed the most inferior potency, NPSCs and BM-MSCs had similar regenerative capacity and located in the middle. All in all, our study showed that CESCs might act as an efficient seed cell source for NP tissue engineering, which paved a new way for the biological solution of disc degeneration diseases.

Clinical efficacy of three different minimally invasive procedures for far lateral lumbar disc herniation.

BACKGROUND: Far lateral lumbar disc herniation (FLLDH) accounts for 2.6% to 11.7% of all lumbar herniated discs. Numerous surgical approaches have been described for treating this condition. The purpose of this study was to evaluate minimally invasive surgical techniques for the treatment of FLLDH. METHODS: From June 2000 to March 2006, 52 patients with FLLDH were treated with minimally invasive procedures. All patients were assessed by anteroposterior and lateral roentgenography and computed tomography (CT). Some patients underwent myelography, discography, and magnetic resonance imaging. Procedures performed included Yeung Endoscopy Spine System (YESS) (n = 25), METRx MicroDiscectomy System (n = 13), and X-tube (n = 14). Patients were followed up for a mean of 13.5 months. Clinical outcomes were assessed using a visual analog scale (VAS) and Nakai criteria. RESULTS: All 3 procedures significantly improved radiating leg symptoms (P < 0.005). After surgery, 84.0%, 84.6%, and 92.8% of patients in the YESS, METRx, and X-tube groups had excellent or good outcomes. There were no statistically significant differences of VAS scores between the groups. The YESS procedure was associated with the shortest operation time, simplest anesthesia, and least trauma compared with the other 2 procedures, especially for type I herniations. The METRx procedure was the most suitable for type II herniations and posterior endoscopic facetectomy. Posterior lumbar interbody fusion and unilateral pedicle screw instrumentation with X-tube was the most suitable for herniations combined with degenerative lumbar instability (type III). CONCLUSION: Minimally invasive strategies and options should be determined with reference to the type of FLLDH.

Effect of vascular endothelial growth factor 121 adenovirus transduction in rabbit model of femur head necrosis.

BACKGROUND: Our objective was to observe the role of vascular endothelial growth factor (VEGF) 121 gene transfer in promoting vascular reconstruction and bone repair in femur head necrosis of rabbits. METHODS: The femoral head necrosis model was induced by injection with ethanol. The necrotic femoral head was transfected with a human adenoviral vector expressing VEGF (Ad-hVEGF121). Bone formation in the subchondral necrotic region was analyzed using histology, by measuring the bone mineral density value, and by observing bone trabecular morphology using image analysis. RESULTS: Revascularization level, bone formation rate, bone quality and quantity, and mineralization level in the subchondral necrotic region of the gene transfection group were significantly higher than the control groups. The control groups had more subchondral bone resorption compared with the gene transfection group. CONCLUSION: VEGF might promote bone formation and revascularization in the subchondral necrotic region of the femoral head, indirectly protecting the necrotic bone trabecula from absorption and avoiding a reduction in the mechanical function of the subchondral region.

[Clinical study on lumbar spondylolisthesis treated by minimally invasive transforaminal lumbar interbody fusion].

OBJECTIVES: To retrospectively analyze the treatment of lumbar spondylolisthesis using minimally invasive and open transforaminal lumbar interbody fusion (TLIF), and compare the clinical results of two techniques. METHODS: From June 2006 to May 2010, 371 patients with lumbar spondylolisthesis grade 1 and 2 were treated with TLIF, pedicle screw fixation and followed up. The mean age was 50.4 years (range, 37 - 85 years). There were 172 patients who underwent minimally invasive TLIF and percutaneous pedicle screw fixation were set as the MIS-TLIF group, 199 patients who underwent open TLIF and pedicle screw fixation were set as the OTLIF group. The operative time, blood loss, X-ray exposure time and complications were compared between the two groups. Clinical outcome was assessed using the visual analog scale (VAS) and the Oswestry disability index (ODI). Fusion rates were determined by using CT scan reconstruction and dynamic lumbar radiography in last fellow-up. RESULTS: The average follow-up duration was 32.7 months with a range of 12-58 months. The gender, age, classification of spondylolisthesis and level of fusion showed a identical pattern in both groups. The mean intra-operative blood loss (310 ± 75) ml and postoperative blood loss (38 ± 13) ml in MIS-TLIF group were significantly superior to the intra-operative blood loss (623 ± 156) ml and postoperative blood loss (184 ± 72) ml in OTLIF group (t = 2.836 and 3.274, P < 0.01). Comparing with the OTLIF group (20 ± 10) s, the MIS-TLIF group had a significantly longer radiation time (51 ± 19) s (t = 2.738, P < 0.01). There was no statistical difference in operating time, lower back pain VAS scores, ODI scores and incidence of complication between the two groups. CONCLUSIONS: Comparing with open TLIF, minimally invasive TLIF is a safe and reliable procedure for treatment of lumbar spondylolisthesis grade 1 and 2 with potential advantages.