Biodegradable magnesium (Mg) materials are considered ideal as osteosynthesis implants. However, clinical application has proven complex. This is primarily associated with the issue of reducing the extent of implant degradation to a range acceptable for the human body, while simultaneously enhancing osteogenesis or osteoinduction. In the present study, a combination of Mg ions and low-intensity pulsed ultrasound (LIPUS) treatment was applied in hFOB 1.19 human osteoblast cells as a potential strategy to resolve this issue. A total of 7,314 differentially expressed genes (DEGs) and 826 shared DEGs in hFOB1.19 osteoblast cells were identified by microarray analysis following treatment with Mg and/or LIPUS. Gene Ontology analysis demonstrated that among cells treated with a combination of Mg and LIPUS, DEGs were significantly enriched in various functional annotations, including ‘wound healing’, ‘transforming growth factor beta receptor signaling pathway’, ‘transcription, DNA-templated’, ‘receptor complex’, ‘nucleus’, ‘SMAD protein complex’, ‘DNA binding’, ‘metal ion binding’ and ‘GTPase activator activity’. Notably, the transforming growth factor (TGF)-β, mitogen-activated protein kinase (MAPK) and tumor necrosis factor (TNF) signaling pathways were preferentially overrepresented in the Mg and LIPUS combination group, which was subsequently confirmed by reverse transcription-quantitative polymerase chain reaction. Furthermore, genes involved in osteoblast mineralization promotion, including bone morphogenetic protein 6, noggin, bone morphogenetic protein receptor (BMPR)1A, BMPR2 and SMAD 5/8, were significantly upregulated following combination treatment compared with the control group. Genes involved in the promotion of migration, including c-Jun N-terminal kinase, doublecortin, paxillin and Jun proto-oncogene AP-1 transcription factor subunit, were also upregulated in the combination treatment group compared with the control group. The DEG data were supported by morphological observations of the osteoblasts using alizarin red S staining and wound healing assays, which indicated that Mg and LIPUS combinative treatment had a synergistic effect on osteoblast mineralization and migration. Additionally, the combined treatment significantly upregulated metal transporter genes associated with Mg entry, including ATPase Na+/K+-transporting subunit α1, cyclin and CBS domain divalent metal cation transport mediator 2, K+ voltage-gated channel subfamily J member 14, transient receptor potential cation channel (TRP) subfamily M member 7 and TRP subfamily V member 2. In summary, the findings of the present study revealed that combined stimulation with Mg and LIPUS may exhibit a synergistic effect on human osteoblast bone formation through the TGF-β, MAPK and TNF signaling pathways, while also facilitating Mg influx. The present study demonstrated the potential of combinative LIPUS and Mg treatment as a novel therapeutic strategy for enhancing the osteoinduction, biocompatibility and biosafety of biodegradable Mg implants.
To investigated morphological variability of vertebral artery (VA) origin and its entrance level into cervical transverse foramina by computed tomography angiography (CTA). To retrospectively investigated CTA of 223 subjects (446 VA courses). Investigated were origin of the VA and its level of entrance into vertebral transverse foramen with notification of the sex and side of variation. The VA entered the C6 transverse process in 91.70% of specimens (409 out of 446 VA courses). Abnormal entrance of VA was observed in 8.30% of specimens (37 VA courses), with the level of entrance into the C3, C4, C5, or C7 transverse foramen at 0.22%, 2.47%, 4.71% and 0.90% respectively. Comparably, the overall variability of abnormal origin of VA was 1.57% (7 out of 466 VA courses), in which the left vertebral arteries all arose from aortic arch. The variation rate of vertebral entrance rose up to 50% in abnormal origin subgroup. When comparing subgroups of subjects with normal and abnormal origin, there was significance difference in the frequency of entrance variation in the level of transverse foramen (p < 0.001). Abnormal entrance and origin of VA were observed in 8.30% and 1.57% of VA courses, which can be accurately appeared by CTA. Regarding to the subgroups of abnormal origin, the frequency of entrance variation was significantly increased in the level of transverse foramen compared to that of normal origin.
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