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Science Advances May 2024Trauma rapidly mobilizes the immune response of surrounding tissues and activates regeneration program. Manipulating immune response to promote tissue regeneration shows...
Trauma rapidly mobilizes the immune response of surrounding tissues and activates regeneration program. Manipulating immune response to promote tissue regeneration shows a broad application prospect. However, the understanding of bone healing dynamics at cellular level remains limited. Here, we characterize the landscape of immune cells after alveolar bone injury and reveal a pivotal role of infiltrating natural killer T (NKT) cells. We observe a rapid increase in NKT cells after injury, which inhibit osteogenic differentiation of mesenchymal stem cells (MSCs) and impair alveolar bone healing. is up-regulated in NKT cells after injury. Systemic administration of CXCL2-neutralizing antibody or genetic deletion of improves the bone healing process. In addition, we fabricate a gelatin-based porous hydrogel to deliver NK1.1 depletion antibody, which successfully promotes alveolar bone healing. In summary, our study highlights the importance of NKT cells in the early stage of bone healing and provides a potential therapeutic strategy for accelerating bone regeneration.
Topics: Bone Regeneration; Animals; Natural Killer T-Cells; Mice; Osteogenesis; Chemokine CXCL2; Mesenchymal Stem Cells; Cell Differentiation; Mice, Inbred C57BL
PubMed: 38758783
DOI: 10.1126/sciadv.adl6343 -
International Journal of Tryptophan... 2024Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is crucial in maintaining the skeletal system. Our study focuses on encapsulating the role of... (Review)
Review
Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is crucial in maintaining the skeletal system. Our study focuses on encapsulating the role of AhR in bone biology and identifying novel signaling pathways in musculoskeletal pathologies using the GEO dataset. The GEO2R analysis identified 8 genes (CYP1C1, SULT6B1, CYB5A, EDN1, CXCR4B, CTGFA, TIPARP, and CXXC5A) involved in the AhR pathway, which play a pivotal role in bone remodeling. The AhR knockout in hematopoietic stem cells showed alteration in several novel bone-related transcriptomes (eg, Defb14, ZNF 51, and Chrm5). Gene Ontology Enrichment Analysis demonstrated 54 different biological processes associated with bone homeostasis. Mainly, these processes include bone morphogenesis, bone development, bone trabeculae formation, bone resorption, bone maturation, bone mineralization, and bone marrow development. Employing Functional Annotation and Clustering through DAVID, we further uncovered the involvement of the xenobiotic metabolic process, p450 pathway, oxidation-reduction, and nitric oxide biosynthesis process in the AhR signaling pathway. The conflicting evidence of current research of AhR signaling on bone (positive and negative effects) homeostasis may be due to variations in ligand binding affinity, binding sites, half-life, chemical structure, and other unknown factors. In summary, our study provides a comprehensive understanding of the underlying mechanisms of the AhR pathway in bone biology.
PubMed: 38757095
DOI: 10.1177/11786469241246674 -
BMC Medicine May 2024Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics,...
BACKGROUND
Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear.
METHODS
Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics.
RESULTS
From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells.
CONCLUSIONS
Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.
Topics: Osteosarcoma; Tumor Microenvironment; Humans; Single-Cell Analysis; Bone Neoplasms; Lymph Nodes; Lymphatic Metastasis; Transcriptome; Animals; Mice; Cell Line, Tumor; Gene Expression Profiling
PubMed: 38755647
DOI: 10.1186/s12916-024-03319-w -
Journal of Orthopaedic Surgery and... May 2024This study aims to evaluate the optimal ratio of synthetic bone graft (SBG) material and platelet rich fibrin (PRF) mixed in a metal 3D-printed implant to enhance bone...
BACKGROUND
This study aims to evaluate the optimal ratio of synthetic bone graft (SBG) material and platelet rich fibrin (PRF) mixed in a metal 3D-printed implant to enhance bone regeneration.
METHODS
Specialized titanium hollow implants (5 mm in diameter and 6 mm in height for rabbit; 6 mm in diameter and 5 mm in height for pig) were designed and manufactured using 3D printing technology. The implants were divided into three groups and filled with different bone graft combinations, namely (1) SBG alone; (2) PRF to SBG in 1:1 ratio; (3) PRF to SBG in 2:1 ratio. These three groups were replicated tightly into each bone defect in distal femurs of rabbits (nine implants, n = 3) and femoral shafts of pigs (fifteen implants, n = 5). Animal tissue sections were obtained after euthanasia at the 8th postoperative week. The rabbit specimens were stained with analine blue, while the pig specimens were stained with Masson-Goldner's trichrome stain to perform histologically examination. All titanium hollow implants were well anchored, except in fracture specimens (three in the rabbit and one fracture in the pig).
RESULT
Rabbit specimens under analine blue staining showed that collagen tissue increased by about 20% and 40% in the 1:1 ratio group and the 2:1 ratio group, respectively. Masson-Goldner's trichrome stain results showed that new bone growth increased by 32% in the 1:1 ratio PRF to SBG, while - 8% in the 2:1 ratio group.
CONCLUSION
This study demonstrated that placing a 1:1 ratio combination of PRF and SBG in a stabilized titanium 3D printed implant resulted in an optimal increase in bone growth.
Topics: Animals; Printing, Three-Dimensional; Rabbits; Platelet-Rich Fibrin; Bone Regeneration; Swine; Titanium; Femur; Bone Substitutes; Bone Transplantation; Prostheses and Implants
PubMed: 38755635
DOI: 10.1186/s13018-024-04784-y -
Nature Communications May 2024The natural history of multiple myeloma is characterized by its localization to the bone marrow and its interaction with bone marrow stromal cells. The bone marrow...
The natural history of multiple myeloma is characterized by its localization to the bone marrow and its interaction with bone marrow stromal cells. The bone marrow stromal cells provide growth and survival signals, thereby promoting the development of drug resistance. Here, we show that the interaction between bone marrow stromal cells and myeloma cells (using human cell lines) induces chromatin remodeling of cis-regulatory elements and is associated with changes in the expression of genes involved in the cell migration and cytokine signaling. The expression of genes involved in these stromal interactions are observed in extramedullary disease in patients with myeloma and provides the rationale for survival of myeloma cells outside of the bone marrow microenvironment. Expression of these stromal interaction genes is also observed in a subset of patients with newly diagnosed myeloma and are akin to the transcriptional program of extramedullary disease. The presence of such adverse stromal interactions in newly diagnosed myeloma is associated with accelerated disease dissemination, predicts the early development of therapeutic resistance, and is of independent prognostic significance. These stromal cell induced transcriptomic and epigenomic changes both predict long-term outcomes and identify therapeutic targets in the tumor microenvironment for the development of novel therapeutic approaches.
Topics: Multiple Myeloma; Humans; Chromatin Assembly and Disassembly; Tumor Microenvironment; Cell Line, Tumor; Mesenchymal Stem Cells; Gene Expression Regulation, Neoplastic; Transcription, Genetic; Bone Marrow Cells; Cell Movement; Stromal Cells; Female; Male
PubMed: 38755155
DOI: 10.1038/s41467-024-47793-5 -
Nature Communications May 2024The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance...
The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.
Topics: Fibroins; Bone Regeneration; Animals; Tissue Scaffolds; Male; Osteogenesis; Mesenchymal Stem Cells; Rats; Magnesium; Biocompatible Materials; Osteoblasts; Cell Differentiation; Rats, Sprague-Dawley; Water; Cell Proliferation; Tissue Engineering; Skull; Cell Adhesion; Bombyx
PubMed: 38755128
DOI: 10.1038/s41467-024-48417-8 -
Physiological Research May 2024Bone remodeling is energetically demanding process. Energy coming from nutrients present in the diet contributes to function of different cell type including...
Bone remodeling is energetically demanding process. Energy coming from nutrients present in the diet contributes to function of different cell type including osteoblasts, osteocytes and osteoclasts in bone marrow participating in bone homeostasis. With aging, obesity and osteoporosis the function of key building blocks, bone marrow stromal cells (BMSCs), changes towards higher accumulation of bone marrow adipose tissue (BMAT) and decreased bone mass, which is affected by diet and sex dimorphism. Men and women have unique nutritional needs based on physiological and hormonal changes across the life span. However, the exact molecular mechanisms behind these pathophysiological conditions in bone are not well-known. In this review, we focus on bone and BMAT physiology in men and women and how this approach has been taken by animal studies. Furthermore, we discuss the different diet interventions and impact on bone and BMAT in respect to sex differences. We also discuss the future perspective on precision nutrition with a consideration of sex-based differences which could bring better understanding of the diet intervention in bone health and weight management.
PubMed: 38752771
DOI: No ID Found -
Global Spine Journal May 2024Retrospective cohort study.
Trabecular Bone Remodeling after Posterior Lumbar Interbody Fusion: Comparison of the Osseointegration in Three-Dimensional Porous Titanium Cages and Polyether-Ether-Ketone Cages.
STUDY DESIGN
Retrospective cohort study.
OBJECTIVES
Imaging changes in the vertebral body after posterior lumbar interbody fusion (PLIF) are determined to be trabecular bone remodeling (TBR). This study aimed to investigate the influence of cage materials on TBR and segment stabilization in PLIF by studying image changes.
METHODS
This was a retrospective study reviewing 101 cases who underwent one-level PLIF with three-dimensional porous titanium (3DTi) cages (53 patients) or polyether-ether-ketone (PEEK) cages (48 patients). Computed tomography images obtained 3 months, 1 year, and 2 years postoperatively were examined for TBR, vertebral endplate cyst formation as an instability sign, cage subsidence, and clear zone around pedicle screw (CZPS).
RESULTS
No significant differences in the TBR-positivity rates were observed between the two cages at 3 months, 1 year, and 2 years postoperatively. However, all 3DTi cage segments that were TBR-positive at 3 months postoperatively showed no CZPS and fewer final instability segments than the TBR-negative segments (0% vs 9%). In contrast, although the PEEK cage segments that were TBR-positive at 3 months postoperatively were not associated with future segmental stabilization, those that were TBR-positive at 1 year postoperatively had fewer final instability segments than the TBR-negative segments (0% vs 33%).
CONCLUSIONS
The 3DTi cage segments with TBR 3 months postoperatively showed significant final segmental stabilization, whereas TBR at 1 year rather than 3 months postoperatively was useful in determining final segmental stabilization for the PEEK cage segments. The timing of TBR, a new osseointegration assessment, were associated with the cage material.
PubMed: 38752287
DOI: 10.1177/21925682241255686 -
Orthopedic Reviews 2024Traditionally, pediatric femoral fracture treatment favored conservative methods, relying on casting and the inherent bone remodeling ability in immature bones. Surgical...
BACKGROUND
Traditionally, pediatric femoral fracture treatment favored conservative methods, relying on casting and the inherent bone remodeling ability in immature bones. Surgical intervention was deferred until age 6, as nonoperative approaches often resulted in complications. Titanium elastic nailing (TENS) emerged as an effective treatment for diaphyseal femoral fractures in ages 6 to 16. However, the choice between TENS and stainless steel elastic nailing (SSENS) remains debated due to inconsistent findings.
OBJECTIVE
This study aimed to evaluate the effectiveness of both nailing systems in pediatric long bone fractures.
METHODS
A retrospective chart review at William Beaumont Hospital Royal Oak included 83 patients aged 6 to 16 treated with TENS or SSENS between January 2011 and January 2021. Data collected encompassed nail related issues, time to fracture union, full weight bearing, and nail removal.
RESULTS
In the TENS group (n=29), the average age was 8.8±2.4 years, and the average BMI was 17.2±3.4. The SSENS group (n=54) had an average age of 9.3±2.7 and an average BMI of 19.7±8.4. Time to fracture union for TENS was 93.8±60.5 days, while SSENS was 82.2±40.0 days.
CONCLUSION
This study found no statistically significant differences in nail-related complications, time to fracture union, full weight bearing, or nail removal between TENS and SSENS in pediatric long bone fractures. The choice between these systems should be based on individual circumstances. Limitations include a small sample size and the study's retrospective nature.
PubMed: 38751450
DOI: 10.52965/001c.116898 -
JPMA. the Journal of the Pakistan... Apr 2024To evaluate the effect of subcutaneous teriparatide therapy on fracture healing rate and change in bone mass density in osteoporotic hip fractures. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effect of subcutaneous teriparatide therapy on fracture healing rate and change in bone mass density in osteoporotic hip fractures.
METHODS
The meta-analysis was done from September to December 2022, and comprised literature search on Wanfang, CNKI, VIP, PubMed, Embase, Cochrane Library, and Web of Science databases from the establishment of the respective database till December 2022. The relevant journals of the library of Macao University of Science and Technology, China, were manually searched for randomised controlled trials of teriparatide in the treatment of osteoporotic hip fractures. The shortlisted studies were subjectd to Cochrane Risk of Bias tool and the Jadad Rating Scale. Meta-analysis was done using the RevMan 5.4 software provided by the Cochrane Collaboration Network. Fracture healing rate and bone mineral density were the primary outcome measures, while mortality, adverse events, malformations, complications, subsequent fractures, timed-up-and-go test, visual analogue scale score, and procollagen type I N-terminal propeptide were the secondary outcome measures.
RESULTS
Of the 1,094 articles retrieved, 8(0.7%) randomised controlled trials were analysed. There were 744 patients; 372(50%) in the teriparatide group and 372(50%) in the control group. Fracture healing rate was not significantly different (p=0.82), while bone mineral density was significantly different between the groups (p<0.001). Mortality, adverse events, deformity, and complications were not significantly different (p>0.05), while subsequent fractures, timed-up-and-go score, visual analogue scale score and procollagen type I N-terminal propeptide were significantly different between the groups (p<0.05).
CONCLUSION
The literature did not support teriparatide's ability to improve the healing rate of osteoporotic hip fractures, or to reduce mortality, adverse events, malformations, and complications. In addition, teriparatide could increase bone mineral density of osteoporotic hip fractures and the procollagen type I N-terminal propeptide value, alleviate hip pain, and reduce subsequent fracture rates. This trial is registered with PROSPERO with registration number CRD42022379832.
Topics: Humans; Teriparatide; Osteoporotic Fractures; Bone Density Conservation Agents; Hip Fractures; Bone Density; Fracture Healing; Bone Remodeling; Randomized Controlled Trials as Topic; Peptide Fragments; Procollagen
PubMed: 38751272
DOI: 10.47391/JPMA.9245