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  • Frontiers Media SA  (3)
  • Hu, Xumin  (3)
  • Wang, Qiwei  (3)
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  • Frontiers Media SA  (3)
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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Endocrinology Vol. 13 ( 2022-7-22)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-7-22)
    Abstract: Osteoporosis often occurs with carotid atherosclerosis and causes contradictory calcification across tissue in the same patient, which is called the “calcification paradox”. Circulating monocytes may be responsible for this unbalanced ectopic calcification. Here, we aimed to show how CD14 + monocytes contribute to the pathophysiology of coexisting postmenopausal osteoporosis and carotid atherosclerosis. Methods We comprehensively analyzed osteoporosis data from the mRNA array dataset GSE56814 and the scRNA-seq dataset GSM4423510. Carotid atherosclerosis data were obtained from the GSE23746 mRNA dataset and GSM4705591 scRNA-seq dataset. First, osteoblast and vascular SMC lineages were annotated based on their functional expression using gene set enrichment analysis and AUCell scoring. Next, pseudotime analysis was applied to draw their differentiated trajectory and identify the key gene expression changes in crossroads. Then, ligand–receptor interactions between CD14 + monocytes and osteoblast and vascular smooth muscle cell (SMC) lineages were annotated with iTALK . Finally, we selected calcification paradox-related expression in circulating monocytes with LASSO analysis. Results First, we found a large proportion of delayed premature osteoblasts in osteoporosis and osteogenic SMCs in atherosclerosis. Second, CD14 + monocytes interacted with the intermediate cells of the premature osteoblast and osteogenic SMC lineage by delivering TGFB1 and TNFSF10. This interaction served as a trigger activating the transcription factors (TF) SP1 and NFKB1 to upregulate the inflammatory response and cell senescence and led to a retarded premature state in the osteoblast lineage and osteogenic transition in the SMC lineage. Then, 76.49% of common monocyte markers were upregulated in the circulating monocytes between the two diseases, which were related to chemotaxis and inflammatory responses. Finally, we identified 7 calcification paradox-related genes on circulating monocytes, which were upregulated in aging cells and downregulated in DNA repair cells, indicating that the aging monocytes contributed to the development of the two diseases. Conclusions Our work provides a perspective for understanding the triggering roles of CD14 + monocytes in the development of the calcification paradox in osteoporosis- and atherosclerosis-related cells based on combined scRNA and mRNA data. This study provided us with an elucidation of the mechanisms underlying the calcification paradox and could help in developing preventive and therapeutic strategies.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 2
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-3-23)
    Abstract: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease, with pathological characteristics of bone erosion, inflammation of attachment point, and bone ankylosis. Due to the ossified intervertebral disc and ligament, pedicle subtraction osteotomy (PSO) is one of the mainstream surgeries of AS-related thoracolumbar kyphosis, but the large amount of blood loss and high risk of instrumental instability limit its clinical application. The purpose of our study is to propose a new transpedicular vertebral body compression osteotomy (VBCO) in PSO to reduce blood loss and improve stability. Methods A retrospective analysis was performed on patients with AS-related thoracolumbar kyphosis who underwent one-level PSO in our hospital from February 2009 to May 2019. A total of 31 patients were included in this study; 6 received VBCO and 25 received eggshell vertebral body osteotomy. We collected demographic data containing gender and age at diagnosis. Surgical data contained operation time, estimated blood loss (EBL), and complications. Radiographic data contained pre-operative and follow-up sagittal parameters including chin brow-vertical angle (CBVA), global kyphosis (GK), thoracic kyphosis (TK), and lumbar lordosis (LL). A typical case with L2-PSO was used to establish a finite element model. The mechanical characteristics of the internal fixation device, vertebral body, and osteotomy plane of the two osteotomy models were analyzed under different working conditions. Results The VBCO could provide comparable restoring of CBVA, GK, TK, and LL in the eggshell osteotomy procedure (all p & gt; 0.05). The VBCO significantly reduced EBL compared to those with eggshell osteotomy [800.0 ml (500.0–1,439.5 ml) vs . 1,455.5 ml (1,410.5–1,497.8 ml), p = 0.033]. Compared with the eggshell osteotomy, VBCO showed better mechanical property. For the intra-pedicular screw fixation, the VBCO group had a more average distributed and lower stress condition on both nails and connecting rod. VBCO had a flattened osteotomy plane than the pitted osteotomy plane of the eggshell group, showing a lower and more average distributed maximum stress and displacement of osteotomy plane. Conclusion In our study, we introduced VBCO as an improved method in PSO, with advantages in reducing blood loss and providing greater stability. Further investigation should focus on clinical research and biomechanical analysis for the application of VBCO.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 3
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-5-18)
    Abstract: Chemoresistance is one of the leading causes that severely limits the success of osteosarcoma treatment. Evaluating chemoresistance before chemotherapy poses a new challenge for researchers. We established an effective chemoresistance risk scoring model for prechemotherapy osteosarcoma using single-cell sequencing. Methods We comprehensively analyzed osteosarcoma data from the bulk mRNA sequencing dataset TARGET-OS and the single-cell RNA sequencing (scRNA-seq) dataset GSE162454. Chemoresistant tumor clusters were identified using enrichment analysis and AUCell scoring. Its differentiated trajectory was achieved with inferCNV and pseudotime analysis. Ligand–receptor interactions were annotated with iTALK. Furthermore, we established a chemoresistance risk scoring model using LASSO regression based on scRNA-seq-based markers of chemoresistant tumor clusters. The TARGET-OS dataset was used as the training group, and the bulk mRNA array dataset GSE33382 was used as the validation group. Finally, the performance was verified for its discriminatory ability and calibration. Results Using bulk RNA data, we found that osteogenic expression was upregulated in chemoresistant osteosarcoma as compared to chemosensitive osteosarcoma. Then, we transferred the bulk RNA findings to scRNA-seq and noticed osteosarcoma tumor clusters C14 and C25 showing osteogenic cancer stem cell expression patterns, which fit chemoresistant characteristics. C14 and C25 possessed bridge roles in interactions with other clusters. On the one hand, they received various growth factor stimulators and could potentially transform into a proliferative state. On the other hand, they promote local tumor angiogenesis, bone remodeling and immunosuppression. Next, we identified a ten-gene signature from the C14 and C25 markers and constructed a chemoresistant risk scoring model using LASSO regression model. Finally, we found that chemoresistant osteosarcoma had higher chemoresistance risk score and that the model showed good discriminatory ability and calibration in both the training and validation groups ( AUC train = 0.82; AUC valid = 0.84). Compared with that of the classic bulk RNA-based model, it showed more robust performance in validation environment ( AUC valid-scRNA = 0.84; AUC valid-bulk DEGs = 0.54). Conclusions Our work provides insights into understanding chemoresistant osteosarcoma tumor cells and using single-cell sequencing to establish a chemoresistance risk scoring model. The model showed good discriminatory ability and calibration and provided us with a feasible way to evaluate chemoresistance in prechemotherapy osteosarcoma.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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