Despite numerous genetic studies on bone metabolism, understanding of the specific mechanisms is lacking. We developed an efficient screening system to identify novel genes involved in bone metabolism using mutant mouse strains registered with the Exchangeable Gene Trap Clones (EGTC) database. From 1278 trap clones in the EGTC database, 52 candidate lines were selected in the first screening, determined based on "EST profile", "X-gal", "Related article", and "Novel gene". For the second screening, bone morphometric analysis, biomechanical strength analysis, bone X-gal staining, etc. were performed on candidate lines. Forty-two male trap lines (80.8%) showed abnormalities with either bone morphometric analysis or biomechanical strength analysis. In the screening process, X-gal staining was significantly efficient (P = 0.0057). As examples, Lbr and Nedd4 trap lines selected using the screening system showed significant bone decrease and fragility, suggesting a relationship with osteoblast differentiation. This screening system using EGTC mouse lines is extremely efficient for identifying novel genes involved in bone metabolism. The gene trap lines identified as abnormal using this screening approach are highly likely to trap important genes for bone metabolism. These selected trap mice will be valuable for use as novel bio-resources in bone research.
The volume loss of skeletal muscle, including lumbar paravertebral muscles, is negatively correlated with the rate of lumbo-pelvic deformity. Moreover, ectopic fat infiltration with highly expressed adipogenesis promoting genes in the paravertebral muscles may reflect pathology of sarcopenia and may cause age-related lumbo-pelvic deformity.
Epithelial protein lost in neoplasm (EPLIN) is an actin-associated cytoskeletal protein that plays an important role in epithelial cell adhesion. EPLIN has two isoforms: EPLINα and EPLINβ. In this study, we investigated the role of EPLINβ in osteoblasts using EPLINβdeficient (EPLINβ GT/GT ) mice. The skeletal phenotype of EPLINβ GT/GT mice is indistinguishable from the wildtype (WT), but bone properties and strength were significantly decreased compared with WT littermates. Histomorphological analysis revealed altered organization of bone spicules and osteoblast cell arrangement, and decreased alkaline phosphatase activity in EPLINβ GT/GT mouse bones. Transmission electron microscopy revealed wider intercellular spaces between osteoblasts in EPLINβ GT/GT mice, suggesting aberrant cell adhesion. In EPLINβ GT/GT osteoblasts, α-and β-catenins and F-actin were observed at the cell membrane, but OB-cadherin was localized at the perinuclear region, indicating that cadherincatenin complexes were not formed. EPLINβ knockdown in MC3T3-e1 osteoblast cells showed similar results as in calvaria cell cultures. Bone formation markers, such as RUNX2, Osterix, ALP, and Col1a1 mRNA were reduced in EPLINβ knockdown cells, suggesting an important role for EPLINβ in osteoblast formation. In conclusion, we propose that EPLINβ is involved in the assembly of cadherin-catenin complexes in osteoblasts and affects bone formation.
Background
Several clinical and basic studies have shown that an association exists between achieving decompression of the spinal cord within a few hours and neurological recovery, even in patients with complete paralysis due to cervical spine dislocation. This study aimed to clarify the impact of helicopter emergency medical services(HEMS)and craniocervical traction using a halo ring on rapid reduction of lower cervical spine dislocation in rural Japan.
Methods
The success rate of and factors inhibiting closed reduction, time from injury to reduction and functional prognosis of lower cervical spine dislocations treated between July 2012 and January 2020 were retrospectively analysed.
Results
Fourteen patients were transported by HEMS (group H), seven were by ambulances (group A) and two were by themselves. Although the average travelled distance and injury severity score were significantly higher in group H (64.5 km, 28.0) than in group A (24.7 km, 18.6), there was no significant difference in the average time to admission or the time to start craniocervical traction after admission between group H (159.4 min, 52.2 min) and group A (163.6 min, 53.2 min). The urgent traction could be administered for 20 patients. The success rate of closed reduction was 95%, and neurological deterioration following traction was not observed in any cases. The average traction time and weight for reduction were 30.3 min and 16.3 kg, respectively. Patients’ body size and fracture-dislocation types did not significantly affect the traction time or weight. The rate of reduction within 4 h after injury was higher in group H (79%) than in group A (33%). Herniated discs were found at dislocation levels in five patients by magnetic resonance imaging scans performed after closed reduction, and all cases of inner fixation were treated via the posterior approach an average of 5.7 days after admission. After these treatment, three of nine AIS A patients recovered the ability to walk, and all the three patients underwent successful closed reduction within 4 h after injury.
Conclusion
HEMS and highly successful closed reduction considerably contributed to the early reduction of cervical spine dislocation and can potentially improve complete paralysis.
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