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Osteoporosis (OP) is a systemic bone metabolic disease with complicated pathogenesis and is difficult to cure clinically. The regulatory mechanisms of OP are needed to be further investigated. In the present study, we focused on the role of myocardial infarction-associated transcript (MIAT) in OP development and examined the underlying mechanism. The serum expression levels of MIAT in samples from patients with OP and healthy controls were compared using quantitative reverse transcription-PCR (qRT-PCR). The dual-luciferase reporter assay was used to confirm the relationship between MIAT and its potential target microRNA, i.e., miR-150-5p. Moreover, bone marrow-derived mesenchymal stem cells (BMSCs) were cultured and transfected with MIAT shRNA, with or without miR-150-5p inhibitor. EdU staining and colony formation analysis were performed to determine the proliferation ability of these cells. Furthermore, the TUNEL assay and flow cytometry were used to assess BMSC apoptosis. Finally, RT-PCR and Western blot assays were employed to assess the expression of osteogenic differentiation biomarkers. Compared with controls, the expression of MIAT was significantly increased, whereas that of miR-150-5p was markedly decreased in patients with OP. MIAT and miR-150-5p expression levels exhibited a strong negative correlation. Furthermore, osteogenic differentiation indicators were suppressed in serum of OP patients. MIAT was downregulated, and miR-150-5p was upregulated in induced to osteogenic differentiation BMSCs. Furthermore, downregulation of MIAT dramatically promoted osteogenic differentiation, increased proliferation, and inhibited apoptosis in BMSCs; miR-150-5p inhibitor abrogated the effects of MIAT. In conclusion, lncRNA MIAT can regulate the proliferation, apoptosis, and osteogenic differentiation of BMSCs.

Rationale: Intraspinal anesthesia, the most common anesthesia type of orthopedic operation, is regarded as safe and simple. Despite of the rare incidence, puncture related complication of intraspinal anesthesia is catastrophic for spinal cord. Here we present an intradural hematoma case triggered by improper anesthesia puncture. The principal reason of this tragedy was rooted in the neglect of spine deformities diagnosis before anesthesia. To the best of our knowledge, there is no specific case report focusing on the intradural hematoma triggered by improper anesthesia puncture. Patient concerns: Hereby a case of thoracolumbar spinal massive hematoma triggered by intraspinal anesthesia puncture was reported. The presenting complaint of the patient was little neurologic function improvement after surgery at 6-month follow-up. Diagnoses: Emergency MRI demonstrated that massive spindle-like intradural T2-weighted image hypointense signal masses from T12 to S2 badly compressed the dural sac ventrally, and his conus medullaris was at L3/4 intervertebral level with absence of L5 vertebral lamina. Hereby, the diagnoses were congenital spinal bifida, tethered cord syndrome, spine intradural hematoma, and paraplegia. Interventions: Urgent surgical interventions including laminectomy, spinal canal exploration hematoma removal, and pedicle fixation were performed. The patient received both medication (mannitol, mecobalamin, and steroids) and rehabilitation (neuromuscular electric stimulation, hyperbaric oxygen). Outcomes: Postoperation, he had regained only hip and knee flexion at II grade strength. His neurologic function was unchanged until 3 weeks postoperation. Six-month follow-up showed just little neurologic function improvement, and the American Spinal Injury Association grade was C. Lessons: By presenting an intradural hematoma case triggered by improper anesthesia puncture, we shared the treatment experience and discussed the potential mechanism of neurologic compromise. The principal reason for this tragedy is preanesthesia examination deficiency. Necessary radiology examinations must be performed to prevent misdiagnosis for spinal malformation.

Osteoporosis (OP) is a systemic bone metabolic disorder, which negatively affects the quality of life in the elders and postmenopausal females. Healthy volunteers and postmenopausal females with OP were enrolled in the present study. Bone densitometry (BMD) was detected by dual-energy X-ray absorptiometry (DXA). CD14+PBMCs and C2C12 cells were cultured to induce osteoclast differentiation and osteoblast differentiation, respectively. The interaction between miR‑140-3p and PTEN was predicted and verified by TargetScan 7.2 and dual luciferase reporter assay, respectively. miRNA/RNA level and protein level were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. Cell proliferation and apoptosis were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining and flow cytometry, respectively. Cell differentiation of CD14+PBMCs and C2C12 cells were detected by tartrate-resistant acid phosphatase (TRAP) staining and alizarin red staining, respectively. The activity of alkaline phosphatase (ALP) was detected by ALP assay. Differences were observed in age, body mass index (BMI), and BMD between the OP group and the control group. Higher miR‑140-3p level and lower PTEN level were found in PBMCs of OP group compared to control group; there was a negative correlation between them in the serum of OP group. miR-140-3p targeted and downregulated the expression of PTEN. miR-140-3p inhibitor inhibited cell proliferation, differentiation, and promoted cell apoptosis of CD14+PBMCs; while promoted cell proliferation, differentiation and inhibited cell apoptosis of C2C12 cells, by targeting PTEN and inactivating PTEN/PI3K/AKT signaling pathway. These findings suggested a potential therapeutic role of miR-140-3p in the treatment of patients with OP.

MicroRNAs (miRNAs) are small conserved RNAs regulating specific target genes in posttranscriptional levels. They have been involved in multiple processes of tumor progression, including cell proliferation. miR-214-5p (also miR-214*) is a newly identified miRNA, and its functions are largely unknown. In this study, we explore the role of miR-214-5p in the proliferation and invasion of human osteosarcoma (OS) cells. The results showed that miR-214-5p was sharply reduced in OS tissues and cell lines, compared with normal tissues and cell lines. In addition, the miR-214-5p mimic greatly increased the miR-214-5p level and significantly decreased the proliferation and invasion of HOS and G293 OS cells. In contrast, the miR-214-5p inhibitor had a completely opposite effect on the miR-214-5p level, cell proliferation, and cell invasion. Moreover, bioinformatics and luciferase reporter gene assays confirmed that miR-1908 targeted the mRNA 3-UTR region of ROCK1, a characterized tumor promoter in OS. In conclusion, miR-214-5p was identified as a new tumor suppressor, which directly targeted ROCK1 and suppressed proliferation of human OS cells.

RASSF4, a member of the RASSF family, is broadly expressed in normal tissues but often inactivated in human cancers. Despite various studies on RASSF4, its role in osteosarcoma remains unclear. Therefore, in this study, we investigated the effects of RASSF4 expression on osteosarcoma cells and explored the underlying mechanism. The results of our study showed that RASSF4 was lowly expressed in osteosarcoma tissues and cells. RASSF4 overexpression significantly inhibited proliferation, migration, and invasion as well as the EMT process in osteosarcoma cells. Meanwhile, we found that RASSF4 overexpression markedly decreased the protein expression of -catenin, cyclin D1, and c-Myc in osteosarcoma cells. In conclusion, our findings showed that RASSF4 overexpression inhibits proliferation, invasion, EMT, and Wnt signaling pathway in osteosarcoma cells. Thus, RASSF4 may be considered a novel target for osteosarcoma treatment.

Rationale: Traumatic nucleus pulposus sequestration (TNPS) usually occurs concurrently with severe destruction of bone. TNPS combined with a slight thoracolumbar flexion- distraction fracture, triggering a disastrous nerve injury, has rarely been reported. Due to the atypical radiologic manifestations, such a patient can easily be overlooked. Patient concerns: Hereby, we present a TNPS patient as well as a slight thoracolumbar flexion-distraction fracture and serious neurologic symptoms. Diagnoses: T12 spinous process fracture, L1 flexion distraction fracture, thoracolumbar traumatic nucleus pulposuse sequestration and lower limbs incomplete paralysis Interventions: To avoid further neurologic compromise, an urgent laminectomy and exploration of the spinal canal was performed. Outcomes: After decompression OR and 4 months rehabilitation, the patient's neurologic function improved remarkably. Lessons: A slight flexion-distraction fracture following injury is liable to eclipse the concurrence of TPNS. For this patient, a high-resolution MRI was needed to make a definitive diagnosis and guide surgery. Once TPNS has been diagnosed, sufficient decompression and discectomy surgery should be performed without delay.

Studies have shown that miR-145-3p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the mechanism of a tumor suppressor of miR-145-3p. The expressions of miR-194 in osteosarcoma cell lines and tissues were monitored by real-time PCR. The proliferation ability was examined by MTT assay. The apoptosis and autophagy of cells were monitored by flow cytometry and microcopy, respectively. The regulation of miR-145-3p on HDAC4 was determined by luciferase assays and western blot assay. The results showed that miR-145-3p was significantly reduced in the osteosarcoma compared with the normal bone tissue. Overexpression of miR-145-3p significantly attenuated the proliferation and induced the apoptosis and autophagy of osteosarcoma cells. Furthermore, we demonstrated that miR-145-3p has inhibited the malignant behavior of osteosarcoma by down-regulating HDAC4 expression. These findings suggested that miR-145-3p may act as a tumor suppressor in osteosarcoma. MiR-145-3p/HDAC4 may be a novel therapeutic target in treatment of osteosarcoma.

Background context Bulging of ligamentum flavum can happen with the aging process and can lead to compression of the spinal cord and nerves. However, the distribution and the risk factors associated with a missed ligamentum flavum bulge (LFB) are unknown. Purpose The aim was to evaluate the distribution and risk factors associated with missed LFB in the cervical spine. Study design This was a retrospective analysis of kinematic magnetic resonance images (kMRI). Patient sample Patients diagnosed with symptomatic neck pain or radiculopathy between March 2011 and October 2012 were included. Outcome measures The outcome measures were missed LFB and degenerative factors. Methods A total of 200 patients (1,000 cervical segments) underwent upright kMRI in neutral, flexion, and extension postures. The LFB, sagittal cervical angles, disc herniation, disc degeneration, disc height, angular motion, translational motion, age, and gender were recorded. After excluding segments with LFB in neutral and flexion position, Pearson and Spearman correlation coefficients were used to evaluate the relation between the risk factors and missed LFB in the extension position. Results The average depth of LFB was 0.24±0.71 mm at C2–C3, 1.02±1.42 mm at C3–C4, 1.65±1.48 mm at C4–C5, 2.13±1.37 mm at C5–C6, and 1.05±1.54 mm at C6–C7. The distribution of LFB was the most frequent at C5–C6 level (76.58%) followed by C4–C5 (63.06%). Disc herniation, disc degeneration, angular variation, and translational motion were significantly correlated with missed LFB at C4–C5 andC5–C6. Disc degeneration was the only factor significantly correlated with missed LFB at all cervical segments. Conclusions Occurrence and depth of missed LFB was the highest at C4–C5 and C5–C6 compared with other cervical levels. Disc degeneration, disc herniation, angular variation, and translational motion could play a role in the development of LFB at C4–C5 andC5–C6.

Background This study aimed to investigate the bone morphogenetic protein-2 (BMP-2) levels in serum and synovial fluid (SF) of patients with primary knee osteoarthritis (OA) and to exam its correlation with radiographic and symptomatic severity of the disease. Material/methods A total of 37 knee OA patients and 20 healthy controls were enrolled in this study. Knee OA radiographic grading was performed according to the Kellgren-Lawrence (KL) grading system by evaluating X-ray changes observed in anteroposterior knee radiography. Symptomatic severity of the disease was evaluated according to the Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores. BMP-2 levels in serum and SF were determined using enzyme-linked immunosorbent assay. Results Serum BMP-2 level in patients with knee OA was higher than that in healthy controls. Knee OA patients with KL grade 4 showed significantly elevated BMP-2 levels in the serum and SF compared with those with KL grade 2 and 3. Knee OA patients with KL grade 3 had significant higher SF levels of BMP-2 than those with KL grade 2. BMP-2 levels in the serum and SF of knee OA patients were both positively correlated with KL grades and WOMAC scores. Conclusions BMP2 levels in serum and SF were closely related to the radiographic and symptomatic severity of knee OA and may serve as an alternative biochemical parameter to determine disease severity of primary knee OA.

To explore the distribution of Schmorl's nodes (SN) in normal adult lumbar spine and determine the association of lumbar disc degeneration and lumbar spine motion.A total of 1 179 individuals underwent magnetic resonance imaging (MRI) scans. They had an age range of 15-85 years and were grouped by 10 years. The distribution of SNs along lumbar spine and their relationship with age and gender were examined by single factor analysis of variance chi-square test. Spine specialists performed lumbar disc degeneration evaluations through the Pfirrmann's classification system. The relationship between SNs, age group, disc location and overall grades of lumbar disc degeneration were analyzed by multiple Logistic regression.The prevalence of SNs was 28.4%. And SNs were observed more frequently in males than females (34.6% vs 20.2%) (P0.01). No significant inter-group difference existed in the incidence of SNs (P = 0.18). SNs were more common at L2 and L3 vertebral bodies (14.3% vs 14.4%) while least common at S1 vertebral body (1.5%). The highest incidence of SNs was found in discs with degeneration grades III (41.9%) and IV (45.3%). The occurrence of SN, aging and disc location were positively correlated with lumbar disc degeneration grade.With a high incidence in healthy individuals, SNs occur in discs at all degrees of degeneration. And the occurrence of SNs is positively associated with lumbar disc degeneration.

STUDY DESIGN Retrospective radiographical study. OBJECTIVE To define the relationship between the grade of disc degeneration and the motion of the lumbar spine by using kinetic magnetic resonance imaging. SUMMARY OF BACKGROUND DATA Disc degeneration is common after middle age. Lumbar instability has generally been recognized as a potential risk factor of low back pain. However, correlations between the grade of disc degeneration and the motion of the lumbar spine need more investigation. METHODS Kinetic magnetic resonance imaging was performed in 162 patients with symptomatic low back pain without prior history of surgery. The lumbar intervertebral discs were graded by spine surgeons according to the degenerative grading system (grades I-V). Translational motion and angular variation were measured at each segment from L1-L2 through L5-S1. The relationship between the degree of lumbar disc degeneration and extent of lumbar spine mobility was analyzed. RESULTS The translational motion in discs with grade I through IV increased gradually, but decreased with grade V. Compared with other less degenerative grades, grade V discs had significantly decreased total intervertebral translational motion (P < 0.05). The angular variation in discs with grade I through IV was fairly constant, but decreased with grade V. Compared with other degenerative grades (I-IV), grade V discs had significantly decreased total intervertebral translational motion (P < 0.05). For less degenerative grades I and II discs, the L2-L3 and L3-L4 segmental units contributed the majority of total angular mobility of the spine. However, for the severely degenerated segments, grade V discs, the contributions of the L2-L3 and L3-L4 significantly decreased (P < 0.01). CONCLUSION As disc degeneration developed from the normal to an increasingly severe stage, the motion of lumbar spine progressed from the normal stage to an unstable phase with higher mobility and finally to an ankylosed stage where stability was increased. LEVEL OF EVIDENCE 3.

STUDY DESIGN A kinematic magnetic resonance imaging study. OBJECTIVE To investigate the distribution of Schmorl nodes (SNs) in the lumbar spine in healthy adults, and determine the association with lumbar disk degeneration and lumbar spine motion. SUMMARY OF BACKGROUND DATA SNs have been associated with several pathologies of the lumbar spine, although it has been demonstrated that they also occur in the healthy adult population without a clearly identified cause. A thorough understanding of SN distribution may help reveal reasons for their formation. How disk degeneration and lumbar spine motion relate to SNs is poorly understood. METHODS Kinematic magnetic resonance images (0.6 T) were available for 1179 healthy individuals from 15 to 85 years of age. Spine specialists performed computer-based measurements. All parameters were measured and calculated automatically using the eRAD PACS Viewer (eRAD Inc., version 6.2.1.1). Lumbar disk degeneration was documented according to the Pfirrmann classification system. Lumbar spine lordosis was quantified as the angle between the inferior endplate of L1 and superior endplate of S1. The level of significance was defined as P ≤ 0.05. The distribution of SNs along the lumbar spine and their relationship with age and sex was investigated using the single factor analysis of variance χ test. The relationship between SNs, age group, disk location, and overall grades of lumbar disk degeneration were investigated by multiple logistic regression analysis. Lumbar spine motion was compared between patients with and without SNs via independent t test among 585 individuals with qualified kinematic images. Multiple logistic regression analysis was performed on associations of lumbar motion range among the SN population. RESULTS The prevalence of SNs in our study population was 28.4%, and SNs were observed to be present more frequently in males (34.6%) than in females (20.2%) (ρ< 0.01). There was no significant difference in the incidence of SNs between age groups (ρ= 0.18). SNs were more common at the L2 and L3 vertebral bodies (14.3% and 14.4%), whereas SNs were least common at S1 vertebral bodies (1.5%). The highest incidences of SNs presentation was on disks with degeneration grade III (41.9%) and grade IV (45.3%). SN occurrence, aging, and disk location were positively correlated with lumbar disk degeneration grade. The lumbar spine range of motion was significantly different between individuals with and without SNs (31.4° vs. 37.9°, ρ< 0.01). The frequency of SNs was associated with decreased lumbar range of motion in all age groups except 51 to 60 years and 61 to 70 years. CONCLUSION SNs have a high incidence in individuals without persistent lumbar disorders and were found in disks at all degrees of degeneration. SNs occurrence were positively associated with lumbar disk degeneration In addition, the presence of SNs was correlated with decreased overall lumbar motion across all age groups.