Correlations of IL-6 and TGF-ß Gene Polymorphisms and Expressions With Osteoporotic, Thoracolumbar, Vertebral Compression Fracture.

Context: Associations between genes and diseases manifest as the influence of gene expression on disease development as well as the impact of variations in the disease-related genes themselves. It's important to determine the genetic variations that can lead to compressed fractures of osteoporotic, thoracic lumbar vertebrae to develop personalized clinical methods to prevent or delay the disease's development. Objective: The study intended to explore the correlations between the gene polymorphisms and gene expressions of the interleukin-6 (IL-6) gene and the transforming growth factor-beta (TGF-ß) gene and osteoporotic, thoracolumbar, vertebral compression fracture. Design: The research team performed an observational study using data from medical records. Setting: The study took place at Xuzhou Medical University in Xuzhou, China. Participants: Participants were 200 patients with an osteoporotic, thoracolumbar, vertebral compression fracture who had been admitted to the hospital at the university between 2019 and 2021 prior to the study and 200 healthy people The research team divided the participants into two groups. The patients became participants in the disease group, and the healthy individuals became participants in the control group. Outcome Measures: The research team: (1) collected peripheral blood from the two groups, (2) extracted genomic deoxyribonucleic acids (DNAs) from karyocytes, (3) examined the IL-6 and TGF-ß gene polymorphisms, and (4) analyzed and correlated participants' clinical data with the gene polymorphisms and expressions. The team used a quantitative polymerase chain reaction (qPCR) to examine the expression levels of IL-6 and TGF-ß. Results: Compared to the control group, the disease group: (1) had allele distributions that were significantly different at the rs2069829 locus of the IL-6 gene (P < .001) and at the rs3087453 of the TGF-ß gene (P = .004); (2) had significantly higher frequencies of allele T at the rs2069829 locus of the IL-6 gene and of allele G at the rs3087453 locus of the TGF-ß gene; (3) had genotype distributions that were significantly different at the rs2069829 locus (P < .001) and the rs2069857 locus (P = .048) of the IL-6 gene and at the rs3087453 locus (P < .001) of the TGF-ß gene; (4) had frequencies that were significantly higher of the TT genotype at the rs2069829 locus, the CC genotype at the rs2069857 locus, and the GC genotype at the rs3087453 locus of the IL-6 gene and the TGF-ß gene; (5) had dominant models that were significantly different at the rs2069829 locus of the IL-6 gene (P = .009) and at rs3087453 locus of the TGF-ß gene (P = .026) and had a recessive model that was significantly different at the rs2069857 locus of the IL-6 gene (P = .040); (6) had significantly different haplotypes CC (P < .001) and TC (P < .001) at the rs2069829 locus and the rs2069857 locus of the IL-6 gene and a significantly different haplotype AC (P = .011) at the rs1800469 locus and the rs3087453 locus of the TGF-ß gene; (7) had an IL-6 gene polymorphism at the rs2069857 locus that was related to the expression of the IL-6 gene (P < .05) and an expression of the IL-6 gene for participants with the AA genotype that was significantly lower than for other genotypes; (8) had a TGF-ß gene polymorphism at the rs1800469 locus that was associated with the expression of the TGF-ß gene (P < .05), and an expression for participants with the GG genotype that was significantly higher than for other genotypes; (9) had an IL-6 gene polymorphism at the rs2069857 locus with an overt correlation with the genotype of osteoporotic, thoracolumbar, vertebral compression fracture (P < .001). Also, participants in the disease group with the genotype CC mainly had type 2 and 3 fractures, while those with genotype AA primarily had type 0 and 1 fractures. Conclusions: IL-6 and TGF-ß gene polymorphisms and expressions are significantly related to osteoporotic, thoracolumbar, vertebral compression fracture.

Bioinformatics Analysis and Experimental Verification Identify Downregulation of COL27A1 in Poor Segmental Congenital Scoliosis.

BACKGROUND: Congenital scoliosis (CS) represents the congenital defect disease, and poor segmental congenital scoliosis (PSCS) represents one of its types. Delayed intervention can result in disability and paralysis. In this study, we would identify the core biomarkers for PSCS progression through bioinformatics analysis combined with experimental verification. METHODS: This work obtained the GSE11854 expression dataset associated with somite formation in the GEO database, which covers data of 13 samples. Thereafter, we utilized the edgeR of the R package to obtain DEGs in this dataset. Then, GO annotation, KEGG analyses, and DO annotation of DEGs were performed by "clusterProfiler" of the R package. This study performed LASSO regression for screening the optimal predicting factors for somite formation. Through RNA sequencing based on peripheral blood samples from healthy donors and PSCS cases, we obtained the RNA expression patterns and screen out DEGs using the R package DESeq2. The present work analyzed COL27A1 expression in PSCS patients by the RT-PCR assay. RESULTS: A total of 443 genes from the GSE11854 dataset were identified as DEGs, which were involved in BP associated with DNA replication, CC associated with chromosomal region, and MF associated with ATPase activity. These DEGs were primarily enriched in the TGF-ß signaling pathway and spinal deformity. Further, LASSO regression suggested that 9 DEGs acted as the signature markers for somite formation. We discovered altogether 162 DEGs in PSCS patients, which were involved in BP associated with cardiac myofibril assembly and MF associated with structural constituent of muscle. However, these 162 DEGs were not significantly correlated with any pathways. Finally, COL27A1 was identified as the only intersected gene between the best predictors for somite formation and PSCS-related DEGs, which was significantly downregulated in PSCS patients. CONCLUSION: This work sheds novel lights on DEGs related to the PSCS pathogenic mechanism, and COL27A1 is the possible therapeutic target for PSCS. Findings in this work may contribute to developing therapeutic strategies for PSCS.

Vertebral compression fractures: Still an unpredictable aspect of osteoporosis

Vertebral compression fracture is a hallmark of osteoporosis (OP) and by far the most prevalent fragility fracture. It is well proven that patients who develop a vertebral compression fracture are at substantial risk for additional fractures. Diagnosis is based on adequate clinical evaluation, imaging, and laboratory tests. The imaging of OP and fragility fractures includes conventional radiology to evaluate spinal fractures, bone mineral density (BMD) testing by dual energy x-ray densitometry, quantitative computerized tomography, magnetic resonance imaging, bone scintigraphy (if necessary), and ultrasound. Screening and treatment of individuals with high risk of osteoporotic fracture are cost-effective, but approximately two-thirds of the vertebral compression fractures (VCF) that occur each year are not accurately diagnosed and, therefore, not treated. Evaluation of VCFs, even though they may be asymptomatic, seems essential to health-related and/or clinical research on OP.

Identification of the molecular mechanism and diagnostic biomarkers in the thoracic ossification of the ligamentum flavum using metabolomics and transcriptomics.

BACKGROUND: To establish a metabolite fingerprint of ossification of the thoracic ligamentum flavum (OTLF) patients using liquid chromatography-mass spectrometry (LC-MS) in combination with transcriptomic data and explore the potential molecular mechanism of pathogenesis. RESULTS: The study cohort was composed of 25 patients with OTLF and 23 healthy volunteers as a control group. Thirty-seven metabolites were identified out by UPLC-MS including uric acid and hypoxanthine. Nine metabolites, including uric acid and hypoxanthine, were found with a Variable Importance in Projection (VIP) score over 1 (p < 0.05). Pathway enrichment indicated that purine metabolism pathways and the other four metabolism pathways were enriched. Transcriptomic data revealed that purine metabolism have a substantial change in gene expression of OTLF and that xanthine dehydrogenase (XDH) is the key regulatory factor. Receiver operating characteristic (ROC) analysis indicated that 17 metabolites, including uric acid, were found with an AUC value of over 0.7. CONCLUSION: Uric acid might be the potential biomarker for OTLF and play an important role within the detailed pathway. XDH could affect purine metabolism by suppressing the expression of hypoxanthine and xanthine leading to low serum levels of uric acid in OTLF, which could be a focal point in developing new therapeutic methods for OTLF.

miR-29a-5p Targets SATB2 and Regulates the SIRT1/Smad3 Deacetylation Pathway to Inhibit Thoracic Ligamentum Flavum Cell Osteogenesis.

STUDY DESIGN: Experimental analysis of the thoracic ligamentum flavum cell osteogenic differentiation process. OBJECTIVE: This study aimed to explore the role of miR-29a-5p and special AT-rich sequence-binding protein 2 (SATB2) in a pathological osteogenic process. SUMMARY OF BACKGROUND DATA: Thoracic ossification of the ligamentum flavum (TOLF) is an uncommon disease wherein ligaments within the spine undergo progressive ossification, resulting in stenosis of the spinal canal and myelopathy. MiR-29a-5p was found to be downregulated in ligament cells from ossified ligament tissue in a previous study. However, whether miR-29a-5p is involved in the process of TOLF has not been investigated. METHODS: The expression of miR-29a-5p in ligament tissues or in the context of TOLF osteogenic cell differentiation was measured via qRT-PCR. Alkaline phosphatase activity assay and Alizarin red staining were used to analyze cellular osteogenesis. The protein-level expression of SATB2, SIRT1, and Smad3 were measured via immunohistochemistry or western blotting. Dual luciferase reporter assays and western blotting were used to confirm that miR-29a targets SATB2. RESULTS: SATB2 was found to be upregulated and miR-29a-5p was downregulated in TOLF tissue. We additionally observed decreased miR-29a-5p expression during the process of TOLF osteogenic cell differentiation, and there was a marked reduction in the expression of key mediators of osteogenesis when miR-29a-5p was overexpressed. Consistent with this, when miR-29a-5p was inhibited this led to enhanced osteogenic cell differentiation of these cells. We further found miR-29a-5p to directly target and suppress the expression of SATB2. Knock-down of SATB2 was sufficient to reduce the ability of miR-29a-5p to inhibit osteogenesis, and this also led to decreased SIRT1 expression and Smad3 acetylation. CONCLUSION: Together our findings indicate that miR-29a-5p is able to prevent thoracic ligamentum flavum cell osteogenesis at least in part via targeting SATB2 and thereby suppressing the SIRT1/Smad3 deacetylation pathway. LEVEL OF EVIDENCE: N/A.

The COL6A1 rs201153092 single nucleotide polymorphism, associates with thoracic ossification of the posterior longitudinal ligament.

Thoracic ossification of the posterior longitudinal ligament (T­OPLL) is one of the most common factors that causes thoracic spinal stenosis, resulting in intractable myelopathy and radiculopathy. Our previous study reported that the rs201153092 polymorphism present in the collagen 6A1 (COL6A1) gene was a potentially pathogenic locus for the development of T­OPLL. The present study aimed to determine whether the rs201153092 mutation causes abnormal expression of COL6A1 in Han Chinese patients with T­OPLL, and to examine the effects of this mutation on osteogenesis by establishing a model of osteogenic differentiation. COL6A1 gene mutant and wild­type mouse 3T3­E1 embryonic osteoblast models were constructed to induce the differentiation of these cells into osteoblasts. The potential of the mutation site to induce abnormal expression of the COL6A1 gene and osteogenic markers was assessed via reverse transcription­quantitative PCR and western blot analyses. The results demonstrated that the rs201153092A mutation site resulted in significantly increased COL6A1 gene expression levels in the OPLL tissues obtained following clinical surgery. This mutation was shown to play an important role in the development of T­OPLL by regulating the overexpression of the COL6A1 gene and significantly increasing the expression levels of osteogenic markers. The findings of the present study suggested that the rs201153092A mutant variant could increase the expression levels of COL6A1 and consequently play a role in the pathogenesis of T­OPLL.

Predominance and homogeneity patterns of physiological FDG accumulation in thoracic and lumbar vertebrae: suspected mechanism of "bone pseudometastasis" on FDG-PET in Japanese patients with esophageal cancer.

OBJECTIVE: False-positive bone lesions (bone pseudometastases) have been often reported in patients with esophageal cancer (EsoC). This study aimed to evaluate the vertebral 2-deoxy-2-[18F] fluoro-D-glucose (FDG) accumulation pattern in patients with newly diagnosed esophageal cancers and other malignancies (OtherT) to elucidate the possible mechanism that causes bone pseudometastasis. METHODS: FDG positron emission tomography/computed tomography performed for 90 patients with EsoC, and 112 patients with OtherT was retrospectively evaluated. The uptake pattern in the thoracic (Th) and lumbar (L) vertebrae was visually assessed regarding predominance (TL, Th ≒ L; Td, Th > L; Ld, L > Th), main intensity compared with the uptake in the blood pool (BP) (Grade 1 < BP, Grade 2 ≒ BP, or Grade 3 > BP), and homogeneity (homogeneous, heterogeneous, marginal, or spotty). The patterns between EsoC and OtherT and between Th and L were compared. RESULTS: TL, Td, and Ld patterns were observed in 51.1%, 48.9%, and 0% in EsoC and 79.7%, 20.3%, and 0% in OtherT. Though Grade 2 was most frequently observed in both groups, the ratio of Grade 3 in Th and Grade 1 in L was significantly higher in EsoC than in OtherT. Heterogeneous and spotty patterns were more frequently observed in L and in EsoC, and these were strongly associated with Td pattern. CONCLUSION: Td pattern was frequently seen, especially in EsoC, and was strongly associated with a heterogeneous or marginal pattern in the L. Heterogeneous marrow distribution with declined lumbar uptake is suspected as the mechanism of bone pseudometastasis.

Vitamin D Deficiency/Insufficiency Is Associated with Risk of Osteoporotic Thoracolumbar Junction Vertebral Fractures.

BACKGROUND The association between serum vitamin D level and vertebral fracture (VFx) remains controversial. The purpose of this study was to determine whether serum 25-hydroxy vitamin D (25(OH)D) level is associated with osteoporotic thoracolumbar junction VFx in elderly patients. MATERIAL AND METHODS From Jan 2013 to Dec 2017, this retrospective case-control study included 534 patients with primary osteoporotic thoracolumbar junction VFx (T10-L2) and 569 elderly orthopedic patients with back pain (without osteoporotic VFx) as controls. Serum 25(OH)D levels were measured and the association with osteoporotic VFx was analyzed. Other clinical data, including BMI, comorbidities, and bone mineral density (BMD), were also collected and compared between these 2 groups. RESULTS It was shown that 25(OH)D levels were significantly lower in patients with T10-L2 VFx than in control patients. Among 534 VFx patients, 417 (78.1%) patients showed grade 2-3 fracture. Serum 25(OH)D levels were significantly related to affected vertebral numbers and VFx severities. The VFx risk was 28% lower (OR=0.72, 95% CI 0.62-0.83) per increased SD in serum 25(OH)D. Compared with the 1st quartile (mean 25(OH)D: 29.67±6.18 nmol/L), the VFx risk was significantly lower in the 3rd (mean 25(OH)D: 60.91±5.12nmol/L) and 4th quartiles (mean 25(OH)D: 103.3±44.21nmol/L), but not in the 2nd quartile (mean 25(OH)D: 45.40±3.95 nmol/L). In contrast, the VFx risk was significantly increased in the 1st quartile (OR=1.87, 95% CI 1.42-2.45) compared with the 2nd-4th quartiles. CONCLUSIONS Vitamin D deficiency/insufficiency was associated with risk of osteoporotic thoracolumbar junction vertebral fractures in elderly patients.

Combined intravoxel incoherent motion diffusion-weighted MR imaging and magnetic resonance spectroscopy in differentiation between osteoporotic and metastatic vertebral compression fractures.

PURPOSE: Our purpose was to combine intravoxel incoherent motion diffusion-weighted MR imaging (IVIM-DWI) and magnetic resonance spectroscopy (MRS) to differentiate osteoporotic fractures from osteolytic metastatic vertebral compression fractures (VCFs). METHODS: A total of 70 patients with VCFs were included and divided into two groups, according to their causes of fractures based on pathological findings or clinical follow-up. All patients underwent conventional sagittal T1WI, T2WI, STIR, IVIM-DWI, and single-voxel MRS. The diffusion coefficient (D), pseudo diffusion (D*), and perfusion fraction (f) parameters from IVIM-DWI and the lipid water ratio (LWR) and fat fraction (FF) parameters from MRS were obtained and compared among groups. Furthermore, the diagnostic performance of MRS, IVIM-DWI, and IVIM-DWI combined with MRS for differentiation between osteoporotic and osteolytic metastatic VCFs was assessed by using receiver operating characteristic (ROC) curve analysis. RESULTS: Compared with the osteoporotic group, the metastatic group had significantly lower values for f, D, and FF, but higher D* (all P < 0.05). The area under the receiver operating characteristic (ROC) curve of MRS, IVIM-DWI, and IVIM-DWI combined with MRS were 0.73, 0.88, and 0.94, respectively. Among these, the IVIM-DWI combined with MRS showed the highest sensitivity, specificity, and accuracy, which are 90.63% (29/32), 97.37 % (37/38), and 94.29% (66/70), respectively. CONCLUSIONS: IVIM-DWI combined with MRS can be more accurate and efficient for differentiation between osteoporotic and osteolytic metastatic VCFs than single MRS or IVIM-DWI.

Identification of a homozygous frameshift variant in RFLNA in a patient with a typical phenotype of spondylocarpotarsal synostosis syndrome.

Spondylocarpotarsal synostosis syndrome, a rare syndromic skeletal disorder characterized by disrupted vertebral segmentation with vertebral fusion, scoliosis, short stature, and carpal/tarsal synostosis, has been associated with biallelic truncating mutations in the filamin B gene or monoallelic mutations in the myosin heavy chain 3 gene. We herein report the case of a patient with a typical phenotype of spondylocarpotarsal synostosis syndrome who had a homozygous frameshift mutation in the refilin A gene (RFLNA) [c.241delC, p.(Leu81Cysfs*111)], which encodes one of the filamin-binding proteins. Refilins, filamins, and myosins play critical roles in forming perinuclear actin caps, which change the nuclear morphology during cell migration and differentiation. The present study implies that RFLNA is an additional causative gene for spondylocarpotarsal synostosis syndrome in humans and a defect in forming actin bundles and perinuclear actin caps may be a critical mechanism for the development of spondylocarpotarsal synostosis syndrome.

Description of an ultrasound-guided thoracic paravertebral block technique and the spread of dye in dog cadavers.

OBJECTIVES: To describe an ultrasound-guided thoracic paravertebral block and determine the distribution after injection of two volumes of methylene blue in dog cadavers. STUDY DESIGN: Prospective experimental cadaveric study. ANIMALS: Twelve dog cadavers weighing 11 ± 3 kg. METHODS: Ultrasound-guided injections aimed at the fifth thoracic (T5) paravertebral space were performed in randomized order using 0.1 or 0.3 mL kg-1 dye solution (six dogs for each volume). Anatomic dissections determined dye spread characteristics, including the presence and degree of staining of spinal nerves, and the presence of intercostal and sympathetic trunk spread. Staining of mediastinum, epidural, intrapleural and contralateral thoracic paravertebral space was recorded. RESULTS: There was no significant difference in dye distribution between groups. The use of anatomic landmarks resulted in the inaccurate identification of the T5 paravertebral space. The T4, T5 and T6 paravertebral spaces were injected in four, five and three of 12 dogs, respectively. Complete staining of the spinal nerve of the thoracic paravertebral space injected was observed in 11 of 12 dogs, and partial staining in one dog in the low-volume group. Multisegmental distribution was demonstrated with staining of contiguous spinal nerves in one dog in the high-volume group, and multiple segments of intercostal (three dogs) and sympathetic trunk (four dogs) spread in both groups. No mediastinal, epidural, intrapleural or contralateral thoracic paravertebral space staining was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasound-guided injection at the thoracic paravertebral space resulted in staining of the spinal nerve in all dogs. However, T5 paravertebral space was not accurately identified using anatomic landmarks. Dye distribution was not significantly different between the two groups; therefore, the use of the lower-volume and multiple-site injections would be potentially necessary in clinical cases to achieve ipsilateral blockade of the thoracic wall.

A Cadaveric Study Investigating the Mechanism of Action of Erector Spinae Blockade.

BACKGROUND AND OBJECTIVES: Erector spinae block is an ultrasound-guided interfascial plane block first described in 2016. The objectives of this cadaveric dye injection and dissection study were to simulate an erector spinae block to determine if dye would spread anteriorly to the involve origins of the ventral and dorsal branches of the spinal nerves. METHODS: In 10 unembalmed human cadavers, 20 mL of 0.25% methylene blue dye was injected bilaterally into the plane between the fifth thoracic transverse process and erector spinae muscle. An in-plane ultrasound-guided technique with the transducer orientated longitudinally was used. During dissection, superficial and deep muscles were identified, and extent of dye spread was documented in cephalocaudal and lateral directions. The ventral and dorsal rami of spinal nerves and dorsal root ganglion at each level were examined to determine if they were stained by dye. RESULTS: There was extensive cephalocaudad and lateral spread of dye deep and superficial to the erector spinae muscles. Except for 1 injection (from 20), the ventral rami were not stained by the dye. In only 2 injections did the dye track posteriorly through the costotransverse foramen to the dorsal root ganglion. In all other cases, the dorsal root ganglia were not involved in the dye injection. The dye stained the dorsal rami posterior to the costotransverse foramen. CONCLUSIONS: There was no spread of dye anteriorly to the paravertebral space to involve origins of the ventral and dorsal branches of the thoracic spinal nerves. Dorsal ramus involvement was posterior to the costotransverse foramen.

Real-time view of anesthetic solution spread during an ultrasound-guided thoracic paravertebral block.

BACKGROUND: Thoracic paravertebral block is a technique for perioperative analgesia in patients undergoing thoracic, chest wall, or breast surgery, or for pain management with rib fractures, which can be performed with or without ultrasound guidance. The ultrasound guidance technique can be used to identify the thoracic paravertebral space, guide needle placement, monitor the spread of local anesthetic (LA) solution, and reduce complications such as pleural puncture and pneumothorax. The possibility of assessing anesthetic spread in real time using ultrasound guidance during paravertebral block offers numerous advantages, including the immediate and accurate identification of the extent of nervous block, with a consequent reduction of LA dose. The real-time visualization of spread may be used to achieve good anesthetic cover by administering the block at a single level, thus reducing complications normally associated with the technique. CASE SUMMARY: This case report describes the use of ultrasound-guided thoracic paravertebral block, at thoracic (T) 4 and 5 levels, in a patient undergoing breast surgery for perioperative analgesia. The authors were able to witness cranial diffusion of LA at T3-T4 in real time, and measure the increase in space between the costotransverse ligament and pleura, as an indication of anesthetic spread, at T2-T3 and T6-T7 levels. CONCLUSIONS: This is the first known case in the literature of direct viewing of LA diffusion in a paravertebral space other than the one in which the block is administered and may open important scenarios for the improvement of anesthesia technique.

Effects of age and weight on the metabolic activities of the cervical, thoracic and lumbar spines as measured by fluorine-18 fluorodeoxyglucose-positron emission tomography in healthy males.

OBJECTIVE: This study aimed to explore the age and weight-related metabolic trends in the spines of healthy male subjects using fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging. SUBJECTS AND METHODS: Forty three healthy male subjects (age 23-75 years, weight 50-145kg) were selected from the CAMONA study. A global assessment methodology was applied to the subjects' 18F-FDG 180 minute scans, where each region of the spine (cervical, thoracic and lumbar) was individually encapsulated in a single region of interest, and standardized uptake value (SUVmean) was calculated per respective region. RESULTS: SUVmean increased significantly with weight in both the thoracic spine (Slope=0.0066, P=0.001) and lumbar spine (Slope=0.0087, P<0.0001), but not the cervical spine. There were no significant correlations between age and SUVmean in all three regions. The cervical spine (average SUVmean=1.84±0.31) illustrated elevated activity when compared to the thoracic (average SUVmean=1.46±0.27, P<0.0001) and lumbar (average SUVmean=1.41±0.28, P<0.0001) spines. CONCLUSION: This study illustrated the ability of 18F-FDG PET to assess metabolic processes in the spine. The data provided evidence of weight dependent metabolic activity, likely related to inflammation. This study offers a methodological precedent that can be applied to studies in populations with back pain.

Physiological uptake of 18F-FDG in the vertebral bone marrow in healthy adults on PET/CT imaging.

BACKGROUND: 18F-fluorodeoxyglucose *Equal contributors. positron emission tomography/computed tomography (18F-FDG PET/CT) has proven to be a valuable imaging modality for the assessment of bone marrow condition. PURPOSE: To investigate the physiological uptake of 18F-FDG in the vertebral bone marrow in healthy adults on PET/CT imaging, and correlate the appearance with clinical factors including gender, body mass index, and age. MATERIAL AND METHODS: A total of 64 healthy individuals underwent PET/CT scan, and for each vertebral body, the mean and maximum standardized uptake value (SUVmean and SUVmax) were determined in the central slice of vertebral body on the transversal fused PET/CT image. For each individual, the FDG uptake of the four regions was obtained by averaging the SUVmean and SUVmax of the vertebrae in individual regions. RESULTS: The FDG uptake from thoracic to sacral vertebrae showed an upward trend first, then a downward trend, while that of cervical vertebrae was relatively stable. The SUVmax and SUVmean values of bone marrow in the old group (age ≥ 50 years) were significantly lower than those in the young group (age < 50 years) in all regions of the spine ( P < 0.05). FDG uptake of the whole spine showed significant negative correlation with age, and the strongest correlation was observed in lumbar spine (SUVmean: r = -0.364, P < 0.05; SUVmax: r = -0.344, P < 0.05). CONCLUSION: FDG uptake showed a tendency to increase first then decrease from thoracic to sacral vertebrae while the tendency was not obvious in cervical vertebrae. In addition, the glycolytic metabolism of all the four regions decreased with advancing age.

Effects of mTOR/NF-κB signaling pathway and high thoracic epidural anesthesia on myocardial ischemia-reperfusion injury via autophagy in rats.

We investigated the role of mammalian target of rapamycin/nuclear factor-kappa B (mTOR/NF-κB) signaling pathway in high thoracic epidural anesthesia (HTEA) against myocardial ischemia-reperfusion (I/R) injury in rats. The rat model of myocardial I/R injury was established. Ninety rats were divided into the normal, sham, I/R, eHTEA, the PDTC, and HTEA + PDTC groups. ELISA was applied to detect cardiac function indexes. HE staining was conducted to observe histopathological changes of myocardial tissues, and TTC staining was performed to detect the myocardial infarction size. TUNEL staining was adopted to detect the cell apoptosis rate. The mRNA and protein levels of mTOR, NF-κB, Fasl, Bcl-2 and Bax, and LC3-I, LC3-II, BNIP3, and Atg5 were detected by RT-qPCR and Western blotting, respectively. The findings indicated that compared with the normal and sham groups, the I/R, PDTC, and HTEA groups showed the larger myocardial infarction size and increased cell apoptosis rate, while the results in the HTEA + PDTC group were opposite. Compared with the normal and sham groups, the I/R group showed reduced mRNA and protein levels of Bcl-2, LC3, BNIP3, and Atg5, and elevated mRNA and protein levels of mTOR, p50, p65, Bax, and Fasl, while the HTEA + PDTC group revealed the opposite results, and the PDTC and HTEA group revealed the increased mRNA and protein levels of Bcl-2, LC3, BNIP3, Atg5, mTOR, p50, p65, Bax, and Fasl. These results prove that the inhibition of mTOR/NF-κB signaling pathway potentiates HTEA against myocardial IR injury by autophagy and apoptosis in rats.

Indeterminate Dendritic Cell Tumor in Thoracic Spine: A Case Report.

BACKGROUND: Indeterminate dendritic cell tumor (IDCT) is an extremely rare hematologic disorder with poorly understood pathogenesis. Occasionally encountered by hematologists, unusual presentations of IDCT have not been reported in the spine literature. METHODS: We report a 51-year-old man who presented with a 3-month history of progressively worsening axial thoracic back pain radiating to his sides. Magnetic resonance imaging revealed a 3-cm enhancing mass at the T9 vertebral body with an exophytic component causing significant canal stenosis. Initial percutaneous biopsy revealed histiocytic sarcoma. RESULTS: The patient underwent exploratory thoracotomy and en bloc resection of the lesion with T8-10 fusion. Final pathology results revealed IDCT with fibrosis. IDCT immunostaining was partially positive for Langerhans cell marker (positive for S100 and CD1a, but lacked Birbeck granules and Langerin stain) and partially positive for blastic plasmacytoid dendritic cell neoplasm. Additionally, it was positive for CD45, CD68, and CD163. Lymphadenopathy was absent in this patient. CONCLUSIONS: Although first reported in the 1980s, IDCT has been omitted from most classifications owing to its rarity. Hematologists have debated the cell of origin; it is believed to comprise pre-Langerhans cells, as Birbeck granules are acquired after migration to the epidermis. IDCT remains of indeterminate origin. We report the first case of spinal IDCT. Familiarity with the histologic features is warranted to ensure accurate diagnosis and appropriate treatment.

Effects of human parathyroid hormone on bone morphogenetic protein signal pathway following spinal fusion in diabetic rats.

Osteoporosis is a major complication in patients with diabetes mellitus. Thus, it is crucial to study the signal mechanisms responsible for enhancement of bone mass in diabetes. Administration of human parathyroid hormone (hPTH) has been reported to prevent osteoblast apoptosis and have anabolic effects on bone in animals and humans. In the present study, we examined the effects of hPTH on expression of bone morphogenetic protein type 2 (BMP-2) and its receptor BMPR2 in diabetic rats following spinal fusion. Our data show that hPTH amplified BMP-2 and BMPR2 in bone tissues of non-diabetic rats, but not in diabetic rats. Our data further demonstrate that hPTH plays a role in regulating BMP-2 and BMPR2 via mTOR-PI3K signal pathway. We suggest specific signaling pathways by which hPTH regulates BMP-2 via mTOR-PI3K mechanism in bone formation following spinal fusion. Notably, our data indicate under diabetic conditions this signal pathway is impaired, thereby likely affecting bone formation after spinal fusion. The subsequent induction of BMP-2 and BMPR2 are likely a part of the protective effects aimed at attenuating pathological bone damage as a result of diabetes.

A histomorphometric study of the cancellous spinal process bone in adolescent idiopathic scoliosis.

PURPOSE: Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity with increased risk of osteopenia of unknown etiology. This study examined the dynamic histomorphometry of AIS patients to gain insight into the underlying pathogenesis of bone metabolism changes in AIS. METHODS: Bone histomorphometry of the spinous process of the 12th thoracic vertebra was analyzed in 33 AIS patients and compared to age-matched normative data. Patients were classified into bone turnover subgroups, based on bone formation rate. RESULTS: Bone volume was subnormal in 67% of AIS patients, but normal in 33%. Bone turnover was high in 76% of the patients, normal in 9%, and low in 15%. Compared to those in the low-turnover group, the high-turnover group patients were taller and had higher TRAP5b values. CONCLUSIONS: Bone histomorphometry indicated that bone fragility and abnormal bone turnover were common in AIS patients. These abnormalities might contribute to the poor bone status and etiology in AIS.

A postnatal role for embryonic myosin revealed by MYH3 mutations that alter TGFß signaling and cause autosomal dominant spondylocarpotarsal synostosis.

Spondylocarpotarsal synostosis (SCT) is a skeletal disorder characterized by progressive vertebral, carpal and tarsal fusions, and mild short stature. The majority of affected individuals have an autosomal recessive form of SCT and are homozygous or compound heterozygous for nonsense mutations in the gene that encodes the cytoskeletal protein filamin B (FLNB), but a subset do not have FLNB mutations. Exome sequence analysis of three SCT patients negative for FLNB mutations identified an autosomal dominant form of the disease due to heterozygosity for missense or nonsense mutations in MYH3, which encodes embryonic myosin. Cells transfected with the MYH3 missense mutations had reduced TGFß signaling, revealing a regulatory role for embryonic myosin in the TGFß signaling pathway. In wild-type mice, there was persistent postnatal expression of embryonic myosin in the small muscles joining the neural arches of the spine suggesting that loss of myosin function in these muscles contribute to the disease. Our findings demonstrate that dominant mutations in MYH3 underlie autosomal dominant SCT, identify a postnatal role for embryonic myosin and suggest that altered regulation of signal transduction in the muscles within the spine may lead to the development of vertebral fusions.