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The Bone & Joint Journal Jul 2024Given the possible radiation damage and inaccuracy of radiological investigations, particularly in children, ultrasound and superb microvascular imaging (SMI) may offer...
AIMS
Given the possible radiation damage and inaccuracy of radiological investigations, particularly in children, ultrasound and superb microvascular imaging (SMI) may offer alternative methods of evaluating new bone formation when limb lengthening is undertaken in paediatric patients. The aim of this study was to assess the use of ultrasound combined with SMI in monitoring new bone formation during limb lengthening in children.
METHODS
In this retrospective cohort study, ultrasound and radiograph examinations were performed every two weeks in 30 paediatric patients undergoing limb lengthening. Ultrasound was used to monitor new bone formation. The number of vertical vessels and the blood flow resistance index were compared with those from plain radiographs.
RESULTS
We categorized the new bone formation into three stages: stage I (early lengthening), in which there was no obvious callus formation on radiographs and ultrasound; stage II (lengthening), in which radiographs showed low-density callus formation with uneven distribution and three sub-stages could be identified on ultrasound: in Ia punctate callus was visible; in IIb there was linear callus formation which was not yet connected and in IIc there was continuous linear callus. In stage III (healing), the bone ends had united, the periosteum was intact, and the callus had disappeared, as confirmed on radiographs, indicating healed bone. A progressive increase in the number of vertical vessels was noted in the early stages, peaking during stages IIb and IIc, followed by a gradual decline (p < 0.001). Delayed healing involved patients with a prolonged stage IIa or those who regressed to stage IIa from stages IIb or IIc during lengthening.
CONCLUSION
We found that the formation of new bone in paediatric patients undergoing limb lengthening could be reliably evaluated using ultrasound when combined with the radiological findings. This combination enabled an improved assessment of the prognosis, and adjustments to the lengthening protocol. While SMI offered additional insights into angiogenesis within the new bone, its role primarily contributed to the understanding of the microvascular environment rather than directly informing adjustments of treatment.
Topics: Humans; Child; Retrospective Studies; Male; Female; Child, Preschool; Adolescent; Ultrasonography; Osteogenesis; Bone Lengthening; Bony Callus; Leg Length Inequality; Microvessels; Radiography
PubMed: 38945540
DOI: 10.1302/0301-620X.106B7.BJJ-2023-1019.R2 -
The Journal of Pediatrics Jun 2024To investigate the extent of extra-skeletal manifestations along with inpatient outcomes and complications associated with osteogenesis imperfecta (OI).
National Trends in Inpatient Hospital Outcomes of Children with Osteogenesis Imperfecta and the Importance of Extra-skeletal Manifestations: A Kids' Inpatient Database Study.
OBJECTIVE
To investigate the extent of extra-skeletal manifestations along with inpatient outcomes and complications associated with osteogenesis imperfecta (OI).
STUDY DESIGN
This cross-sectional study utilized the Kids' Inpatient Database (KID) as part of the Healthcare Cost and Utilization Project (HCUP) to investigate inpatient hospital outcomes and management in patients with OI from 1997 through 2016. Data regarding hospital characteristics, cost of treatment, inpatient outcomes, and procedures were collected and analyzed.
RESULTS
There were 7,291 admissions that listed OI as a diagnosis in the KID database from 1997 through 2016. Unexpectedly, over one third of all admissions in these children with OI presented with an extra-skeletal manifestation. The rate of major complications was 3.85%. The rate of minor complications was 19.4%, most commonly respiratory problems. Mortality rate was 18.2 % in the neonatal period and 1.0% in all other admissions. Total charges of hospital stay increased over the years.
CONCLUSION
We identified a striking prevalence of extra-skeletal manifestations in OI along with inpatient outcomes and complications associated with OI, of which respiratory complications were predominant. We observed a significant financial burden for patients with OI and identified additional risks for financial crisis, in addition to disparities in care identified among socioeconomic groups. These data contribute to a more holistic understanding of OI from diagnosis to management.
PubMed: 38945443
DOI: 10.1016/j.jpeds.2024.114174 -
Archives of Oral Biology Jun 2024This systematic review aims to evaluate existing evidence to investigate the therapeutic efficacy of M2 macrophage-derived exosomes in bone regeneration. (Review)
Review
OBJECTIVE
This systematic review aims to evaluate existing evidence to investigate the therapeutic efficacy of M2 macrophage-derived exosomes in bone regeneration.
DESIGN
A comprehensive search between 2020 and 2024 across PubMed, Web of Science, and Scopus was conducted using a defined search strategy to identify relevant studies regarding the following question: "What is the impact of M2 macrophage-derived exosomes on bone regeneration?". Controlled in vitro and in vivo studies were included in this study. The SYRCLE tool was used to evaluate the risk of bias in the included animal studies.
RESULTS
This review included 20 studies published. Seven studies were selected for only in vitro analysis, whereas 13 studies underwent both in vitro and in vivo analyses. The in vivo studies employed animal models, including 163 C57BL6 mice and 73 Sprague-Dawley rats. Exosomes derived from M2 macrophages were discovered to be efficacious in promoting bone regeneration and vascularization in animal models of bone defects. These effects were primarily confirmed through morphological and histological assessments. This remarkable outcome is attributed to the regulation of multiple signaling pathways, as evidenced by the findings of 11 studies investigating the involvement of miRNAs in this intricate process. In addition, in vitro studies observed positive effects on cell proliferation, migration, osteogenesis, and angiogenesis. Heterogeneity in study methods hinders direct comparison of results across studies.
CONCLUSION
M2 macrophage-derived exosomes demonstrate remarkable potential for promoting bone regeneration. Further research optimizing their application and elucidating the underlying mechanisms can pave the way for clinical translation.
PubMed: 38943857
DOI: 10.1016/j.archoralbio.2024.106034 -
ACS Biomaterials Science & Engineering Jun 2024In addition to transmitting and carrying genetic information, RNA plays an important abiotic role in the world of nanomaterials. RNA is a natural polyanionic...
In addition to transmitting and carrying genetic information, RNA plays an important abiotic role in the world of nanomaterials. RNA is a natural polyanionic biomacromolecule, and its ability to promote osteogenesis by binding with other inorganic materials as an osteogenic induction agent was discovered only recently. However, whether it can promote osseointegration on implants has not been reported. Here, we investigated the effect of the RNA-containing coating materials on peri-implant osseointegration. Total RNA extracted from rat muscle tissue was used as an osteogenic induction agent, and hyaluronic acid (HA) was used to maintain its negative charge. In simulated body fluids (SBF), in vitro studies demonstrated that the resulting material encouraged calcium salt deposition. Cytological experiments showed that the RNA-containing coating induced greater cell adhesion and osteogenic differentiation in comparison to the control. The results of animal experiments showed that the RNA-containing coating had osteoinductive and bone conduction activities, which are beneficial for bone formation and osseointegration. Therefore, the RNA-containing coatings are useful for the surface modification of titanium implants to promote osseointegration.
PubMed: 38943625
DOI: 10.1021/acsbiomaterials.4c00133 -
Calcified Tissue International Jun 2024In 2023 following extensive consultation with key stakeholders, the expert Nosology Working Group of the International Skeletal Dysplasia Society (ISDS) published the... (Review)
Review
In 2023 following extensive consultation with key stakeholders, the expert Nosology Working Group of the International Skeletal Dysplasia Society (ISDS) published the new Dyadic Nosology for Genetic Disorders of the Skeleton. Some 770 entities were delineated associated with 552 genes. From these entities, over 40 genes resulting in distinct forms of Osteogenesis Imperfecta (OI) and Bone Fragility and/or Familial Osteoporosis were identified. To assist clinicians and lay stake holders and bring the considerable body of knowledge of the matrix biology and genomics to people with OI as well as to clinicians and scientists, a dyadic nosology has been recommended. This combines a genomic co-descriptor with a phenotypic naming based on the widely used Sillence nosology for the OI syndromes and the many other syndromes characterized in part by bone fragility.This review recapitulates and explains the evolution from the simple Congenita and Tarda subclassification of OI in the 1970 nosology, which was replaced by the Sillence types I-IV nosology which was again replaced in 2009 with 5 clinical groups, type 1 to 5. Qualitative and quantitative defects in type I collagen polypeptides were postulated to account for the genetic heterogeneity in OI for nearly 30 years, when OI type 5, a non-collagen disorder was recognized. Advances in matrix biology and genomics since that time have confirmed a surprising complexity both in transcriptional as well as post-translational mechanisms of collagens as well as in the many mechanisms of calcified tissue homeostasis and integrity.
PubMed: 38942908
DOI: 10.1007/s00223-024-01248-7 -
Biomedicine & Pharmacotherapy =... Jun 2024In cell-based bone augmentation, transplanted cell dysfunction and apoptosis can occur due to oxidative stress caused by the overproduction of reactive oxygen species...
In cell-based bone augmentation, transplanted cell dysfunction and apoptosis can occur due to oxidative stress caused by the overproduction of reactive oxygen species (ROS). Edaravone (EDA) is a potent free radical scavenger with potential medical applications. This study aimed to investigate the effect of controlling oxidative stress on bone regeneration using EDA. Bone marrow-derived cells were collected from 4-week-old rats, and EDA effects on cell viability and osteogenic differentiation were evaluated. Collagen gels containing PKH26-prelabeled cells were implanted into the calvarial defects of 12-week-old rats, followed by daily subcutaneous injections of normal saline or 500 μM EDA for 4 d. Bone formation was examined using micro-computed tomography and histological staining. Immunofluorescence staining was performed for markers of oxidative stress, macrophages, osteogenesis, and angiogenesis. EDA suppressed ROS production and hydrogen peroxide-induced apoptosis, recovering cell viability and osteoblast differentiation. EDA treatment in vivo increased new bone formation. EDA induced the transition of the macrophage population toward the M2 phenotype. The EDA group also exhibited stronger immunofluorescence for vascular endothelial growth factor and CD31. In addition, more PKH26-positive and PKH26-osteocalcin-double-positive cells were observed in the EDA group, indicating that transplanted cell survival was prolonged, and they differentiated into bone-forming cells. This could be attributed to oxidative stress suppression at the transplantation site by EDA. Collectively, local administration using EDA facilitates bone regeneration by improving the local environment and angiogenesis, prolonging survival, and enhancing the osteogenic capabilities of transplanted cells.
PubMed: 38941894
DOI: 10.1016/j.biopha.2024.117032 -
Journal of Materials Chemistry. B Jun 2024The bone immune microenvironment can influence the occurrence and progression of bone defects. To date, research on promoting macrophage M2 polarization to improve bone...
The bone immune microenvironment can influence the occurrence and progression of bone defects. To date, research on promoting macrophage M2 polarization to improve bone injury repair has been insufficient. In this study, we designed an injectable poly(L-lactic acid) (PLLA) porous microsphere that forms calcium phosphate crystals on its surface by binding to melatonin, followed by bionanomimetic mineralization . The microsphere is injectable and degradable, and its release of melatonin (MT) and calcium phosphate (CaP) crystals promotes macrophage M2 polarization, reprogramming of macrophages, and enhanced osteogenesis. After LPS stimulation, the proportion of M2-polarized macrophages in the MS@CaP@MT group was 39.2 ± 2.7%, significantly higher than that in other groups ( < 0.05). Further, in the MS@CaP@MT group, rats exhibited bone mineral densities of 129.4 ± 12.8 mg cc at 2 weeks and 171.6 ± 13.6 mg cc at 4 weeks in the defect area, which were significantly higher than those in other groups ( < 0.05). Using an animal model of femoral condylar defects, we demonstrated that MT PLLA porous microspheres loaded with calcium phosphate crystals can improve the immune microenvironment and form a microsphere-centered osteogenesis model. This significantly accelerates bone defect repair and provides a potential strategy for bone defect treatment.
PubMed: 38940905
DOI: 10.1039/d3tb02965d -
International Journal of Molecular... Aug 2024Naringenin (NAR) is a prominent flavanone that has been recognized for its capacity to promote the osteogenic differentiation of human periodontal ligament stem cells...
Naringenin (NAR) is a prominent flavanone that has been recognized for its capacity to promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). The present study aimed to explore how NAR promotes the osteogenic differentiation of hPDLSCs and to assess its efficacy in repairing alveolar bone defects. For this purpose, a protein‑protein interaction network of NAR action was established by mRNA sequencing and network pharmacological analysis. Gene and protein expression levels were evaluated by reverse transcription‑quantitative and western blotting. Alizarin red and alkaline phosphatase staining were also employed to observe the osteogenic capacity of hPDLSCs, and immunofluorescence was used to examine the co‑localization of NAR molecular probes and AKT in cells. The repair of mandibular defects was assessed by micro‑computed tomography (micro‑CT), Masson staining and immunofluorescence. Additionally, computer simulation docking software was utilized to determine the binding affinity of NAR to the target protein, AKT. The results demonstrated that activation of the nitric oxide (NO)‑cyclic guanosine monophosphate (cGMP)‑protein kinase G (PKG) signaling pathway could promote the osteogenic differentiation of hPDLSCs. Inhibition of AKT, endothelial nitric oxide synthase and soluble guanylate cyclase individually attenuated the ability of NAR to promote the osteogenic differentiation of hPDLSCs. Micro‑CT and Masson staining revealed that the NAR gavage group exhibited more new bone formation at the defect site. Immunofluorescence assays confirmed the upregulated expression of Runt‑related transcription factor 2 and osteopontin in the NAR gavage group. In conclusion, the results of the present study suggested that NAR promotes the osteogenic differentiation of hPDLSCs by activating the NO‑cGMP‑PKG signaling pathway through its binding to AKT.
Topics: Humans; Osteogenesis; Flavanones; Proto-Oncogene Proteins c-akt; Signal Transduction; Cell Differentiation; Nitric Oxide; Cyclic GMP-Dependent Protein Kinases; Stem Cells; Cyclic GMP; Animals; Male; Cells, Cultured
PubMed: 38940332
DOI: 10.3892/ijmm.2024.5391 -
Frontiers in Pharmacology 2024Although caffeine generally offers benefits to human health, its impact on bone metabolism remains unclear. This study aimed to systematically evaluate the long-term...
Although caffeine generally offers benefits to human health, its impact on bone metabolism remains unclear. This study aimed to systematically evaluate the long-term effects of caffeine administration on osteoclasts, osteoblasts, and ovariectomy-induced postmenopausal osteoporosis (OP). Our findings revealed that 3.125 and 12.5 μg/mL caffeine inhibited RANKL-mediated osteoclastogenesis in RAW 264.7 cells through the MAPK and NF-κB pathways, accompanied by the inactivation of nuclear translocation of nuclear factor NFATc1. Similarly, 3.125 and 12.5 μg/mL of caffeine modulated MC3T3-E1 osteogenesis via the AKT, MAPK, and NF-κB pathways. However, 50 μg/mL of caffeine promoted the phosphorylation of IκBα, P65, JNK, P38, and AKT, followed by the activation of NFATc1 and the inactivation of Runx2 and Osterix, ultimately disrupting the balance between osteoblastogenesis and osteoclastogenesis. studies showed that gavage with 55.44 mg/kg caffeine inhibited osteoclastogenesis, promoted osteogenesis, and ameliorated bone loss in ovariectomized mice. Conversely, long-term intake of high-dose caffeine (110.88 mg/kg) disrupted osteogenesis activity and promoted osteoclastogenesis, thereby disturbing bone homeostasis. Collectively, these findings suggest that a moderate caffeine intake (approximately 400 mg in humans) can regulate bone homeostasis by influencing both osteoclasts and osteoblasts. However, long-term high-dose caffeine consumption (approximately 800 mg in humans) could have detrimental effects on the skeletal system.
PubMed: 38939843
DOI: 10.3389/fphar.2024.1405173 -
BioImpacts : BI 2024This study aimed to assess the potential of poly (acrylic acid)/tricalcium phosphate nanoparticles (PAA/triCaPNPs) scaffold in terms of biocompatibility and...
INTRODUCTION
This study aimed to assess the potential of poly (acrylic acid)/tricalcium phosphate nanoparticles (PAA/triCaPNPs) scaffold in terms of biocompatibility and osteoconductivity properties the in-vivo evaluation as well as to investigate the performance of PAA/triCaPNPs scaffold (with or without exosomes derived from UC-MSCs) for bone regeneration of rat critical-sized defect.
METHODS
PAA/triCaPNPs scaffold was made from acrylic acid (AA) monomer, N,N'-methylenebisacrylamide (MBAA), sodium bicarbonate (SBC), and ammonium persulfate (APS) through freeze-drying method. For evaluation, we randomly divided 24 rats into three groups. The rat calvarial bone defects were treated as follows: (1) Control group: defects without any treatment, (2) scaffold group: defects treated with scaffold only, (3) scaffold+exo group: defects treated with scaffold enriched with exosomes (1 μg/μL, 150 μg per rat). Eight- and 12-weeks post-surgery, half of the animals were sacrificed and bone regeneration was examined through micro-computerized tomography (µ-CT), histological staining, and immunohistochemistry (IHC).
RESULTS
Quantitative analysis based on µ-CT scan images at 8 and 12 weeks post-implantation clearly indicated that healing rate for defects that were filled with scaffold enriched with exosome was significantly higher than defects filled with scaffold without exosome. The H&E and Masson staining results revealed that more new bone-like form developed in the scaffold+exo group than that in control and scaffold groups. Further, IHC staining for osteocalcin and CD31 confirmed that more bone healing in the scaffold+exo group at 12 weeks could be associated with osteogenesis and angiogenesis concurrently.
CONCLUSION
In the present study, we aimed to investigate the therapeutic potential of PAA/triCaPNPs scaffold as a carrier of human UC-MSC-derived exosome to achieve the exosome-controlled release on calvarial bone defect. The results indicated that the exosome-enriched scaffold could effectively minify the defect area and improve the bone healing in rat model, and as such it could be an option for exosome-based therapy.
PubMed: 38938758
DOI: 10.34172/bi.2023.27510