Osteocytes as main responders to Low Intensity Pulsed Ultrasound for the treatment of fracture healing
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ABSTRACT:
PROVIDER: PRJNA682601 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13198751_1.fastq.gz | Fastqsanger.gz | |||
| SRR13198751_2.fastq.gz | Fastqsanger.gz | |||
| SRR13198752_1.fastq.gz | Fastqsanger.gz | |||
| SRR13198752_2.fastq.gz | Fastqsanger.gz | |||
| SRR13198753_1.fastq.gz | Fastqsanger.gz |
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Project description:Skeletal tissue is known to respond to mechanical stress. Ultrasound stimulation is one of mechanical stress and low intensity pulsed ultrasound (LIPUS) devices have been clinically utilized to promote the fracture healing. However, it is still not clear which skeletal cells, especially osteocytes or osteoblasts, mainly respond to LIPUS stimulation and how they contribute to fracture healing. To examine that, we utilized medaka known to have bones without embedded osteocytes and zebrafish known to have bones with embedded osteocytes as an in vivo model. Interestingly, fracture healing was accelerated by ultrasound stimulation in zebrafish but not in medaka. To examine the molecular events induced by LIPUS stimulation in osteocyte, we performed RNA-sequencing with the murine long bone osteocyte Y4 (MLO-Y4) cell line exposed to LIPUS. 179 genes reacted to LIPUS stimulation and functional cluster analysis defined that several molecular signatures related in immunity, secretion and transcription. Especially, most of isolated transcription related genes were modulated by LIPUS also in vivo experiments using zebrafish. Target genes analysis showed that inflammatory response and bone formation in fracture healing could be transcriptionally regulated in osteocytes by LIPUS stimulation. Among these transcription genes, early growth response (Egr) 1,2, JunB, Forkhead box Q1 (FoxQ1) and nuclear factor of activated T cells (NFAT) c1 were not altered by LIPUS in medaka unlike zebrafish suggesting that these genes would be key transcriptional regulator of LIPUS-dependent fracture healing through osteocytes. In this study, we revealed bone-equipped osteocytes is necessary for LIPUS-induced promotion of fracture healing through the transcriptional control of target genes presumably to activate neighboring cells involved in fracture healing event.
2021-05-03 | GSE162674 | GEO
Project description:Ultrasound stimulation is a type of mechanical stress, and low-intensity pulsed ultrasound (LIPUS) devices have been used clinically to promote fracture healing. However, it remains unclear which skeletal cells, in particular osteocytes or osteoblasts, primarily respond to LIPUS stimulation and how they contribute to fracture healing. To examine this, we utilized medaka, whose bone lacks osteocytes, and zebrafish, whose bone has osteocytes, as in vivo models. Fracture healing was accelerated by ultrasound stimulation in zebrafish, but not in medaka. To examine the molecular events induced by LIPUS stimulation in osteocytes, we performed RNA sequencing of a murine osteocytic cell line exposed to LIPUS. 179 genes reacted to LIPUS stimulation, and functional cluster analysis identified among them several molecular signatures related to immunity, secretion, and transcription. Notably, most of the isolated transcription-related genes were also modulated by LIPUS in vivo in zebrafish. However, expression levels of early growth response protein 1 and 2 (Egr1, 2), JunB, forkhead box Q1 (FoxQ1), and nuclear factor of activated T cells c1 (NFATc1) were not altered by LIPUS in medaka, suggesting that these genes are key transcriptional regulators of LIPUS-dependent fracture healing via osteocytes. We therefore show that bone-embedded osteocytes are necessary for LIPUS-induced promotion of fracture healing via transcriptional control of target genes, which presumably activates neighboring cells involved in fracture healing processes.
| S-EPMC8119462 | biostudies-literature
Project description:We performed a comprehensive analysis of gene expression changes following low-intensity pulsed ultrasound (LIPUS) treatment of cultured bone marrow cells under bone formation conditions, using cDNA microarray analysis Bone marrow cells were obtained from the femora of rats and were suspended in an osteogenic medium to make a cell culture. After cultures were established, test cultures were exposed to LIPUS via the base of the cell culture plates for 15 min/day on days 3–9 (LIPUS group). Control cultures (without LIPUS exposure) were otherwise treated identically to the LIPUS group. On day 10, total RNA was extracted from both sets of cultures and hybridized to microarray slides, the data sets were analysed. Markers for differentiated osteoblasts and osteocytes, as well as collagen-related genes, cell adhesion factors were up-regulated in LIPUS group on day 10. Gene expression in response to LIPUS treatment of bone marrow cells were measured on day 10 after cultures were established. Experiments were performed at each conditions (LIPUS or Control).
2015-07-10 | E-GEOD-70662 | biostudies-arrayexpress
Project description:Low-intensity pulsed ultrasound (LIPUS) has been applied as a therapeutic adjunct to promote fracture healing. However, the detailed molecular mechanisms by which LIPUS promotes bone fracture healing have not yet been fully elucidated. In the present study, the early response genes elicited by low-intensity pulsed ultrasound (LIPUS) in bone marrow stromal cells (BMSCs) were investigated using GeneChip® oligonucleotide microarrays.
2019-08-19 | GSE135935 | GEO
Project description:We performed a comprehensive analysis of gene expression changes following low-intensity pulsed ultrasound (LIPUS) treatment of cultured bone marrow cells under bone formation conditions, using cDNA microarray analysis Bone marrow cells were obtained from the femora of rats and were suspended in an osteogenic medium to make a cell culture. After cultures were established, test cultures were exposed to LIPUS via the base of the cell culture plates for 15 min/day on days 3–9 (LIPUS group). Control cultures (without LIPUS exposure) were otherwise treated identically to the LIPUS group. On day 10, total RNA was extracted from both sets of cultures and hybridized to microarray slides, the data sets were analysed. Markers for differentiated osteoblasts and osteocytes, as well as collagen-related genes, cell adhesion factors were up-regulated in LIPUS group on day 10.
2015-07-10 | GSE70662 | GEO
Project description:The main reservoir for Staphylococcus aureus osteomyelitis is the bone tissue where this pathogen can persist and form small colony variants for long periods within osteoblasts and osteocytes. Recently the osteocytes were described as a main reservoir for this pathogen in bone tissue. However, the mechanisms involved in the persistence of S. aureus within these cells are still unknown. Here we investigated the intrinsic relation between S. aureus and both bone cells during infection. The infection of osteoblasts and osteocytes by this pathogen generates the functional bifurcation of these cells into two different responders. Whereas osteoblasts are able to induce a strong antimicrobial respond, the osteocytes trigger signals to recruit immune cells and enhance the inflammation. Moreover, we found that extracellular signals from osteocytes enhance the intracellular bacterial clearance on osteoblasts but not on osteocytes. Even that both cells contain TLR2, the main toll receptor responsible of S. aureus recognition, only osteoblasts were able to increase its expression after infection. Although the expression of TLR2 was not altered in osteocytes, these cells secrete higher lipid mediators and cytokines than osteoblasts. In addition, we found by proteomic analysis that the reduced intracellular bacterial killing of osteocytes is related to a low expression of antimicrobial peptides and reactive oxygen species (ROS) in these cells. Our results suggest that osteocytes contribute to the high inflammation observed in osteomyelitis and at the same time, provide the main niche for S. aureus persistence due to their poor intracellular antimicrobial response. Collectively, these findings reveal the roles of bone cells upon S. aureus infection and provide new insight on the treatment failure of osteomyelitis.
2022-08-02 | PXD029440 | Pride
Project description:Background Treatment of scaphoid nonunion is challenging, leading clinicians to pursue innovation in surgical technique and adjunctive therapies to improve union rates. Purpose The purpose of this study was to investigate the use of low-intensity pulsed ultrasound as an adjunctive treatment modality following surgical treatment of scaphoid nonunion in adolescent patients, for whom this therapy has not yet been FDA-approved. Patients and Methods We performed a retrospective review of adolescent patients with scaphoid nonunion treated surgically followed by adjunctive low-intensity pulsed ultrasound therapy. All patients underwent 20 minutes of daily ultrasound therapy postoperatively until there was evidence of bony healing, based on both clinical and radiographic criteria. Final healing was confirmed by > 50% bone bridging on CT scan. Results Thirteen of fourteen (93%) patients healed at a mean interval of 113 days (range 61-217 days). There were no surgical or postoperative complications. One patient developed heterotopic bone formation about the scaphoid. Conclusions Our study suggests that low-intensity pulsed ultrasound therapy can safely be utilized as an adjunctive modality in adolescents to augment scaphoid healing following surgical intervention. Level of Evidence Level IV, Case series.
| S-EPMC4408126 | biostudies-other
Project description:BackgroundLow-intensity pulsed ultrasonography (LIPUS) is a form of mechanical stimulation that is delivered via a special device to the fracture site for the acceleration of fracture healing. We conducted a meta-analysis to assess the effect of LIPUS for fresh fractures in adults.MethodsMEDLINE, EMBASE and the Cochrane Library searched between Jan 1980 and Nov 2016. Studies should be quasi-randomized and randomized controlled trials (RCTs) comparing treatment with LIPUS to placebo or no treatment in adults with fresh fractures, reporting outcomes such as function; time to union; delayed union or non-union. Summary standard mean difference (SMD) and the risk ratio (RR) with their 95% confidence interval (CI) calculated with a random effects model. I statistic was used to assess the heterogeneity. Risk of bias was assessed by the Cochrane risk-of-bias tool. The GRADE system was used to evaluate the evidence quality.ResultsA total of 12 trials with 1099 patients were included. The pooled results showed that LIPUS significantly reduced the time to fracture union (SMD: 0.65, 95% CI: 1.13 to 0.17), improved the quality of life (SMD: 0.20, 95% CI: 0.03-0.37) without affecting the time to full weight bearing (SMD: 0.76, 95% CI: 1.92 to 0.4), the time to return to work (SMD: 0.06, 95% CI: 0.14 to 0.27), or the incidence rate of delayed union and nonunion (RR: 1.02, 95% CI: 0.60-1.74).ConclusionsModerate-to-high quality evidence shows that LIPUS treatment reduces the time to fracture union and improves the quality of life without affecting functional recovery and incident rate of delayed union and nonunion, suggesting that LIPUS treatment may be a good treatment modality for adults with fresh fractures. However, there are some methodological limitations in the eligible trials, further studies are needed to determine the clinical circumstances under which LIPUS is truly valid and to examine the optimal approach for the use of this adjunctive therapy.
| S-EPMC5626319 | biostudies-literature
Project description:Low-intensity pulsed ultrasound (LIPUS) is a special type of low intensity ultrasound. In periodontal disease, LIPUS was applied as an adjuvant and non-invasive therapeutic treatment. While, the specific mechanism of LIPUS in the treatment of periodontal disease is not quite clear.RAW264.7 cells were induced to M1/M2 macrophage-like polarization by LPS/IL4. LIPUS was performed to stimulate RAW264.7 cells at an intensity of 45 mW/cm2, 25 min, interval 24 h, twice. The polyA mRNA sequencing of LPS induced RAW264.7 cells, LPS induced and LIPUS treated RAW264.7 cells were conducted.Our results suggested that LIPUS played an anti-inflammatory role by inhibiting LPS-induced M1 polarization of RAW264.7 cells in an Wnt2b/AXIN/β-catenin dependent way. LIPUS may inhibit inflammation in periodontal diseases by regulating macrophage differentiation, so as to play a therapeutic role in periodontal diseases.
2024-10-15 | GSE273466 | GEO
Project description:A223 bintrafusp alfa non-responders and responders
| PRJNA677973 | ENA