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IntroductionAccumulating evidence demonstrates that long non-coding RNAs (lncRNAs) are associated with the development of osteoporosis.MethodsThis study aimed to investigate the effects of MALAT1 on osteogenic differentiation and cell apoptosis in osteoporosis. MALAT1 level, detected by RT-qPCR, was downregulated in hindlimb unloading (HU) mice and simulated microgravity (MG)-treated MC3T3-E1 cells. Moreover, osteogenic differentiation-related factor (Bmp4, Col1a1, and Spp1) levels were measured by RT-qPCR and Western blot. ALP activity was detected, and ALP staining was performed. Cell apoptosis was assessed by flow cytometry.ResultsThe results revealed that MALAT1 upregulated the expression of Bmp4, Col1a1, and Spp1, and enhanced ALP activity. Knockdown of MALAT1 suppressed their expression and ALP activity, suggesting that MALAT1 promoted osteogenic differentiation. Additionally, MALAT1 inhibited apoptosis, increased Bax and caspase-3 levels, and decreased Bcl-2 level. However, knockdown of MALAT1 had opposite results. In MG cells, MALAT1 facilitated osteogenic differentiation and suppressed apoptosis. Furthermore, miR-485-5p was identified as a target of MALAT1, and WNT7B was verified as a target of miR-485-5p. Overexpression of miR-485-5p rescued the promotion of osteogenic differentiation and the inhibition of apoptosis induced by MALAT1. Knockdown of WNT7B abolished the facilitation of osteogenic differentiation and the suppression of apoptosis induced by downregulation of miR-485-5p.DiscussionIn conclusion, MALAT1 promoted osteogenic differentiation and inhibited cell apoptosis through the miR-485-5p/WNT7B axis, which suggested that MALAT1 is a potential target to alleviate osteoporosis.

Background: To investigate the therapeutic effect of Hydroxy-safflower yellow A (HSYA) on rat’s osteoporosis and explore its potential mechanism of action.Methods: Bilateral ovariectomized female rats (OVX) were used to establish a postmenopausal rat model of osteoporosis. HSYA was given as an intervention, and estradiol was used as a positive control. The levels of serum alkaline phosphatase (ALP), calcium ion (Ca2+), and inorganic phosphorus (IP) were used to detect bone loss. Three months after modeling, the rats were sacrificed and the rat’s ovaries, kidneys, tibia, and femur were used to calculate the organ index. The bone marrow of the femur of the rats was stained with Giemsa staining. The femur strength of rats was measured by INSTRON. The degree of osteoporosis was detected by pathological staining after decalcification of bone tissue. Predicted the main targets of HSYA in combination with bioinformatics, and the proteins related to osteoclast differentiation were detected in combination with western blotting. The effect of HSYA on the differentiation of RAW264.7 cells into osteoclasts was observed.Results: The Giemsa staining and serum test results showed that the operation was successful and affected bone metabolism. In the bone strength test, HSYA significantly increased the maximum threshold of femoral load in rats. Pathological examination showed that tibial cartilage, trabecular bone, and cortex significantly increased after treatment with HYSA. The number of osteoblasts increased while the number of osteoclasts decreased—elevated levels of type I and III collagen. Autodock was used for molecular docking of potential targets of HSYA. qPCR and western blot were used to show that the expression levels of CA2 and osteoclast differentiation-related proteins were significantly decreased after HSYA treatment. Cell level results showed that HSYA could inhibit the activity of osteoclasts and the ability of RAW264.7 cells to differentiate into osteoclasts.Conclusion: HSYA can inhibit the differentiation and formation of osteoclasts by inhibiting the expression of CA2 and relieving osteoporosis symptoms in OVX rats.

Background: Overexpression or mutated activation of Fibroblast growth factor receptor 3 (FGFR3) is involved in the pathogenesis of many tumors. More and more studies focus on the potential usage of therapeutic antibodies against FGFR3. Results: In this study, a novel single-chain Fv (ScFv) against FGFR3 was prepared and characterized. To achieve the soluble expression, ScFv was fused with Sumo (Small ubiquitin-related modifier) by polymerase chain reaction (PCR), and cloned into pET-20b. The recombinant bacteria were induced by 0.5 mM Isopropyl-β-d-thiogalactopyranoside (IPTG) for 16 h at 20°C, and the supernatant liquid of Sumo-ScFv was harvested and purified by Ni-NTA chromatography. After being cleaved by the Sumo protease, the recombinant ScFv was released from the fusion protein, and further purified by Ni-NTA chromatography. The purity of ScFv was shown to be higher than 95% and their yield reached 4 mg per liter of bacterial culture. In vitro data showed that ScFv can significantly attenuate FGF9-induced phosphorylation of FGFR3. Conclusion: We provide a novel method to produce soluble expression and bioactive functions of ScFv in Escherichia coli.

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 χ² 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 f 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. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective study., Objective: Symptomatic scoliosis can be a source of severe pain and disability. When nonoperative treatments fail, spine fusion is considered as an effective procedure in scoliosis management. The purpose of this study was to evaluate the trends of patients with scoliosis undergoing posterior long segment fusion (PLSF) with and without recombinant human bone morphogenetic protein 2 (rhBMP-2)., Methods: Patients within the orthopedic subset of Medicare database undergoing PLSF from 2005 to 2011 were identified using the PearlDiver Patient Records Database. Both diagnosis and procedural International Classification of Diseases, ninth edition and Current Procedural Terminology codes were used. The year of procedure, age, sex, region, and rhBMP-2 use were recorded., Results: In total, 1,265,591 patients with scoliosis were identified with 29,787 PLSF surgeries between 2005 and 2011. The incidence of PLSF procedures increased gradually from 2005 to 2009, decreased in 2010 (p < 0 0.01), and grew again in 2011. Patients over age 84 years had the highest incidence of PLSF. The lowest incidence of the procedures was in the Northeast, 5.96 per 100,000 patients. Sex differences were observed with a male-to-female ratio of 0.40 (p < 0.01). The use of rhBMP-2 for PLSF increased steadily from 2005 to 2009; the numbers dropped dramatically in 2010 and returned by 2011., Conclusions: According to our study, patients with scoliosis demonstrated a 0.6575 average incidence increase of PLSF treatments annually. There were significant differences in incidence of PLSF procedure and patient demographics. Additionally, rhBMP-2 consumption significantly changed when we stratified it by sex, age, and region respectively.