IRF-1-inhibited lncRNA XIST regulated the osteogenic differentiation via miR-450b/FBXW7 axis.

Osteoporosis influences life quality among elder people. Osteoblast dysfunction could cause the occurrence of osteoporosis. LncRNA XIST are involved in the progression of osteoporosis. However, the correlation between IRF-1 and XIST in osteogenic differentiation remains unclear. In the study, Clinical samples were collected for the analysis of XIST level. mRNA and protein levels were detected by RT-qPCR and western blot, respectively. H&E staining was performed to observe the histological changes in mice. Alizarin Red Staining was applied to assess the calcium deposits in hBMSCs. Meanwhile, the relation among XIST, miR-450b and FBXW7 was investigated by dual luciferase assay and ChIP. In vivo model was constructed to assess the impact of XIST in osteoporosis. XIST was found to be upregulated in osteoporosis, and XIST overexpression could inhibit the osteogenic differentiation in hBMSCs. IRF-1 could transcriptionally inhibit the expression of XIST, and XIST could inhibit osteogenic differentiation through binding with miR-450b in hBMSCs. In addition, miR-450b significantly promoted the osteogenic differentiation in hBMSCs via targeting FBXW7. Furthermore, XIST knockdown could inhibit the symptom of osteoporosis in vivo. IRF-1 promoted the osteogenic differentiation via mediation of lncRNA XIST/miR-450b/FBXW7 axis, and this finding might shed novel insights on exploring new ideas against osteoporosis.

lncRNA MALAT1 promotes osteogenic differentiation through the miR-217/AKT3 axis: A possible strategy to alleviate osteoporosis.

BACKGROUND: Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) are associated with the development of osteoporosis. The present study aimed to investigate the effect of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on osteogenic differentiation in osteoporosis. METHODS: MALAT1 levels were detected by a real-time polymerase chain reaction (RT-qPCR). Moreover, the levels of osteogenic differentiation-related factors (Bmp4, Col1a1 and Spp1) were measured by a RT-qPCR and western blotting. Alkaline phosphatase (ALP) activity was detected using an ALP staining assay. RESULTS: MALAT1 levels were downregulated in hindlimb unloading mice and simulated in microgravity (MG) treated MC3T3-E1 cells. Moreover, MG treatment induced the downregulation of the expression of ALP, BMP4, Col1a1 and Spp1, whereas overexpression of MALAT1 abolished the downregulation. MG also inhibited ALP activity, whereas MALAT1 reversed the effect. Furthermore, miR-217 was identified as a target of MALAT1, and AKT3 was verified as a target of miR-217. Overexpression of miR-217 rescued the promotion of osteogenic differentiation induced by MALAT1 in MG treated cells. Knockdown of AKT3 abolished the facilitation of osteogenic differentiation induced by downregulation of miR-217. CONCLUSIONS: MALAT1 promotes osteogenic differentiation through regulating miR-217/AKT3 axis, suggesting that MALAT1 is a potential target with respect to alleviating osteoporosis.

Resveratrol Promotes Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Through miR-193a/SIRT7 Axis.

Resveratrol (RES) is a novel dietary phenol compound derived from plants and has been studied extensively for its health benefit and medical potential including osteoporosis. The purpose of this study is to investigate the role of resveratrol in osteoporosis in vivo and in vitro and explore the mechanism of osteogenic differentiation of BMSCs. RT-qPCR, ELISA, and Western blot were used to measure the expression level of miR-193a, SIRT7, and osteogenic markers proteins. The interaction between miR-193a and SIRT7 was validated by dual-luciferase reporter assay. Moreover, MTT assay was conducted to detect cell viability. Alizarin red s staining was used to examine bone formation and calcium deposits. The ovariectomized rat model was set up successfully and HE staining was used to examine femoral trabeculae tissue. Our results showed that miR-193a was overexpressed, while SIRT7 was downregulated in osteoporosis. RES suppressed miR-193a to promote osteogenic differentiation. Mechanically, miR-193a targeted and negative regulated SIRT7. Additionally, it was confirmed that SIRT7 promoted osteogenic differentiation of BMSCs through NF-κB signaling pathway. Further study indicated that RES exerted its beneficial function through miR-193a/SIRT7-mediated NF-κB signaling to alleviate osteoporosis in vivo. Our research suggested that the RES-modulated miR-193a inhibition is responsible for the activation of SIRT7/NF-κB signaling pathway in the process of osteogenic differentiation, providing a novel insight into diagnosis and treatment of osteoporosis.

Long noncoding RNA BCAR4 promotes osteosarcoma progression through activating GLI2-dependent gene transcription.

Despite great advances have been made in the understanding of biology of osteosarcoma, the molecular mechanisms involved in osteosarcoma tumorigenesis and progression are still largely unknown. Long noncoding RNA (lncRNA) is a new type of RNA molecule, which plays pivotal roles in many tumors. lncRNA BCAR4 has been identified as an oncogenetic lncRNA involved in the progression of breast cancer. However, the functions and clinical significances of BCAR4 in osteosarcoma are unknown now. In this study, we found that BCAR4 was significantly upregulated in osteosarcoma tissues. Increased expression of BCAR4 was significantly correlated with large tumor size, advanced Enneking stage, lung metastasis, and poor prognosis. Functional experiments demonstrated that knockdown of BCAR4 inhibits the proliferation and migration of osteosarcoma cell in vitro. Consistently, knockdown of BCAR4 inhibits osteosarcoma tumorigenesis and lung metastasis in vivo. Chromatin isolation by RNA purification assay showed that BCAR4 physically associates with the promoters of GLI2 target genes. The depletion of BCAR4 inhibits the expression of GLI2 target genes and GLI2 reporter luciferase activity in a dose-dependent manner. The expression of BCAR4 and GLI2 target genes is significantly correlated in osteosarcoma tissues. Depletion of DLI2 abolished the effects of BCAR4 on osteosarcoma. Taken together, these findings demonstrated that BCAR4 promotes osteosarcoma progression via activating GLI2-dependent gene transcription and serves as a potential prognostic biomarker and a therapeutic target of osteosarcoma.

Beyond Magnification and Illumination: Ergonomics with a 3D Exoscope in Lumbar Spine Microsurgery to Reduce Musculoskeletal Injuries.

OBJECTIVE: The risk of musculoskeletal injuries (MSIs) increases over years of practice which may lead to career-ending among surgeons. Exoscopes represent a new generation of imaging systems that help surgeons operate in a more comfortable posture. This article aimed to assess advantages and limitations, especially ergonomics with a 3D exoscope in lumbar spine microsurgery versus an operating microscope (OM) to reduce MSIs. METHODS: From March 2018 to May 2020, 90 patients with lumbar disc herniation undergoing a single-level minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) procedure were included. Forty-seven patients were operated with the assistance of the exoscope and 43 patients were operated with the assistance of the OM. Clinical data, magnification, and illumination were evaluated. In particular, the ergonomics of surgeons was evaluated by a questionnaire (subjective) and a rapid entire body assessment (REBA; objective). RESULTS: The postoperative outcomes were reasonably well balanced between the two groups. The handling of the exoscope was comparable to that of the OM. The depth perception, image quality, and illumination of the exoscope were inferior to those of the OM in MIS-TLIF with long and deep approaches. The educational and training function of the exoscope was superior to that of the OM. Importantly, surgeons rated the ergonomics of the exoscope as very high on the questionnaire and the REBA to the OM (P = 0.017). CONCLUSIONS: This study showed that the exoscope was a safe and effective alternative to the OM for assisting the MIS-TLIF procedure with the unique advantage of ergonomics to reduce musculoskeletal injuries.

Cervical and First Thoracic Spine Hounsfield Units Assessment and Relationship to Clinical Outcomes and Cervical Sagittal Parameters in Patients Undergoing Anterior Cervical Spine Surgery.

OBJECTIVE: This study had 3 objectives: to compare bone mineral density (BMD) from 3 axial slices, subchondral trabecular bone 2 mm inferior to the cranial endplate, middle of the vertebral body, and subchondral trabecular bone 2 mm superior to the caudal endplate; assess BMD variations and correlations of C1-T1 vertebrae; and correlate BMD with clinical outcomes and cervical sagittal parameters in patients undergoing anterior cervical discectomy and fusion. METHODS: The study enrolled 71 patients who underwent anterior cervical discectomy and fusion between March 2017 and January 2020. Patient demographics, clinical outcomes, cervical sagittal parameters, and Hounsfield units (HUs) of C1-T1 vertebrae were recorded. Analysis of variance was performed to compare HUs from the axial slices. Pearson correlation coefficient was performed to calculate the relationship between mean HUs of C1-T1 and to assess correlations of mean HUs with clinical outcomes and cervical sagittal parameters. RESULTS: There were no significant differences between HUs of 3 axial levels. Mean HUs were highest in the mid-cervical spine (C4). Significant correlations in mean HUs among all measured spinal levels were observed. Age, sex, and body mass index were not related to mean HUs. Visual analog scale, Neck Disability Index, and Patient Health Questionnaire-9 scores were not related to HUs before and after surgery. There were significant correlations among mean HUs of C2-T1 vertebrae, C2-C7 sagittal vertical axis, and cranial tilt. Mean HUs of C4 had the strongest correlation with C2-C7 sagittal vertical axis. CONCLUSIONS: To our knowledge, this is the first study of cranial and caudal subchondral trabecular BMD using HUs and comparing them with the middle of the vertebral body and study of correlations between mean HUs of C1-T1 vertebrae and clinical outcomes and cervical sagittal parameters. Correcting C2-C7 sagittal vertical axis and cranial tilt would improve BMD of C1-T1 vertebrae.

Cervical Spine Microsurgery with the High-Definition 3D Exoscope: Advantages and Disadvantages.

OBJECTIVE: The aim of this study was to evaluate our experience with a high-definition 3-dimensional (3D) exoscope (EX) for cervical spine surgery versus a binocular operating microscope (OM). METHODS: A retrospective review of patients undergoing a single-level anterior cervical discectomy and fusion (ACDF) procedure for the treatment of cervical myelopathy from March 2019 to May 2020 was performed. Demographic, perioperative, and clinical outcomes of 50 patients were included, 23 of whom received assistance from the 3D exoscope (EX group) and 27 of whom received assistance from the OM (OM group). Operative baseline and postoperative outcome parameters were evaluated. Periprocedural handling, visualization, and illumination by the EX, as well as surgeons' ergonomics, were scored using a questionnaire and rapid upper limb assessment (RULA). RESULTS: Baseline characteristics were similar between the 2 groups. There were no significant differences between groups in mean operative time, blood loss, duration of admission, or postoperative improvement of symptoms. Both groups showed similar clinical improvements after surgery. There were no intraoperative complications in either group. According to the attending surgeons, the intraoperative handling of instruments for the EX was rated to be comparable to that of the OM. Surgeons rated the comfort level of the intraoperative posture for the EX as very high on the subjective questionnaire and equal to the OM on the objective RULA. When compared with the OM, depth perception, image quality, and illumination for the EX were rated as inferior in ACDF procedures with long approaches. The operative education and training function of the EX was rated to be superior to that of the OM. CONCLUSIONS: Overall, our study showed that the EX appears to be a safe alternative for common ACDF with the unique advantage of excellent comfort and also serves a useful educational tool for the surgical team. However, our investigation revealed several important limitations of this system, including slightly inferior visualization and illumination quality compared with the OM.

Worldwide Trends of Research on Periprosthetic Osteolysis: A Bibliometric Study Based on VOSviewer.

BACKGROUND: Due to the increasing number of joint arthroplasty operations, surgeons have begun to devote more attention to the problem of periprosthetic osteolysis. In recent years, numerous studies have focussed on periprosthetic osteolysis, but there have been no relevant bibliometric studies. METHODS: We searched the Web of Science database for relevant articles concerning periprosthetic osteolysis published from 1965 to 2021. The following data were extracted: authors' name, article title, publication journal, impact factor (IF) of the journal in the publication year, keywords, topic of the article, publication country/region, the sum of times cited, H-index and funding sources. VOSviewer and Excel 2019 were used to conduct the bibliometric study and visualise the analysis. RESULTS: A total of 1255 publications were included. In all selected articles, "orthopaedics" became the dominant topic (662 of 1255, 52.75%). The most productive years were 2018 and 2019, with a total of 83 publications. The Journal of Arthroplasty published the most articles on periprosthetic osteolysis (110 publications). The United States of America published the most articles (525, 41.83%). The latest keywords "continuous intramedullary infusion", "erythromycin", "autophagy", "bone-resorbing cells" and "proinflammatory cytokines" both appeared in five articles in 2017. CONCLUSION: This bibliometric study showed that there is a growing trend in published articles related to periprosthetic osteolysis. Journal of Arthroplasty was the top productive journal on periprosthetic osteolysis. The United States of America dominates studies of periprosthetic osteolysis. "Continuous intramedullary infusion", "erythromycin", "autophagy", "bone-resorbing cells" and "proinflammatory cytokines" may be new research hotspots in the field of periprosthetic osteolysis.

Clinical and radiological outcomes in three-dimensional printing assisted revision total hip and knee arthroplasty: a systematic review.

BACKGROUND: This study investigates whether three-dimensional (3D) printing-assisted revision total hip/knee arthroplasty could improve its clinical and radiological outcomes and assess the depth and breadth of research conducted on 3D printing-assisted revision total hip and knee arthroplasty. METHODS: A literature search was carried out on PubMed, Web of Science, EMBASE, and the Cochrane Library. Only studies that investigated 3D printing-assisted revision total hip and knee arthroplasty were included. The author, publication year, study design, number of patients, patients' age, the time of follow-up, surgery category, Coleman score, clinical outcomes measured, clinical outcomes conclusion, radiological outcomes measured, and radiological outcomes conclusion were extracted and analyzed. RESULTS: Ten articles were included in our review. Three articles investigated the outcome of revision total knee arthroplasty, and seven investigated the outcome of revision total hip arthroplasty. Two papers compared a 3D printing group with a control group, and the other eight reported 3D printing treatment outcomes alone. Nine articles investigated the clinical outcomes of total hip/knee arthroplasty, and eight studied the radiological outcomes of total hip/knee arthroplasty. CONCLUSION: 3D printing is being introduced in revision total hip and knee arthroplasty. Current literature suggests satisfactory clinical and radiological outcomes could be obtained with the assistance of 3D printing. Further long-term follow-up studies are required, particularly focusing on cost-benefit analysis, resource availability, and, importantly, the durability and biomechanics of customized prostheses using 3D printing compared to traditional techniques.

[Total knee arthroplasty for the treatment of hemophilic arthropathy of the knee].

OBJECTIVE: To study the efficacy of total knee anhmplasty (TKA) for the treatment of hemophilic knee arthropathy, and to explore the operative characteristics, the selection of prothesis, the effectiveness and safety of clotting factor replacement treatment. METHODS: From January 2008 to June 2010, 10 patients (12 knees)with hemophilic anhropathv underwent TKA. The average age was 33.6 years old (ranged, 17 to 49 years). There was 8 cases of type A hemophilia and 2 cases of type B hemophilia. According to Arnold and Hilgartner classification: 7 knees were IV degree and 5 knees were V degree. The level of VIII factor for replacement treatment was more than 80% on operation day, more than 60% within 3 days after operation, more than 40% from the third day to the second week after operation. Added prothrombin complex concentrate (PCC) to improve the level of IX factor, and the level of IX factor for replacement treatment was more than 40% on operation day, more than 30% within 3 days after operation, more than 20% from the third day to the second week after operation. Functional training was mainly based on continuous passive motion (CPM) device after surgery. Clinical assessment included hospital for special surgery knee score (HSS) and the individual scores (including pain, function, activity, muscle strength, flexion deformity and stability). RESULTS: Ten patients (12 knees) were followed-up, and the average duration was 11 months (ranged, 6 to 24 months). The average preoperative HSS score was (44.9 +/- 12.5) (ranged, 29 to 62 scores), whereas the average postoperative HSS score was (84.4 +/- 10.2) (ranged 72 to 96 scores) (P < 0.01). The preoperative individual score including pain, function, activity, muscle strength flexion deformity and stability were significantly improved compared with pre-operation, the differences between them were statistically significant (P < 0.01 ). TKA had the distinct role in relieving pain from preoperative (8.5 +/- 4.1) to postoperative (24.5 +/- 4.4). CONCLUSION: Under the strict perioperative coagulation factor replacement therapy, TKA is a safe and an effective treatment for hemophmc anhmpathy of knee joint, whicht can effectively relieve pain and improve joint function.