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Gene May 2024Steroid-induced osteonecrosis of the femoral head (SONFH) is a disease characterized by a collapsed femoral head caused by the overuse of glucocorticoids. Dysfunction of...
Preliminary study on the mechanism by which exosomes derived from human exfoliated deciduous teeth improve the proliferation and osteogenic inhibitory effect of glucocorticoid-induced BMSCs.
BACKGROUND
Steroid-induced osteonecrosis of the femoral head (SONFH) is a disease characterized by a collapsed femoral head caused by the overuse of glucocorticoids. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) is an important pathological feature of SONFH. In this study, we investigated whether exosomes from SHEDs (stem cells from human exfoliated deciduous teeth) have a therapeutic effect on glucocorticoid-induced inhibition of proliferation and osteogenesis in BMSCs, and elucidated the underlying mechanisms involved.
METHODS
Primary dental pulp cells were isolated and cultured from human deciduous tooth pulp, SHEDs were isolated and purified by the limiting dilution method and exosomes were isolated from the supernatants of SHEDs by ultracentrifugation. The cell surface markers CD31, CD34, CD45, CD73, CD90 and CD105 were detected by flow cytometry. A Cell-Counting-Kit-8 assay was used to detect cell activity. ALP and Alizarin Red staining were used to identify osteogenic differentiation ability, and exosomes were identified using transmission electron microscopy, NanoFCM and Western blotting. PKH67 fluorescence was used to track the uptake of exosomes by BMSCs. Transcriptome analysis combined with quantitative real-time PCR was used to explore the underlying mechanism involved.
RESULTS
Exosomes secreted by SHEDs can be endocytosed by BMSCs, and can partially reverse the inhibitory effects of glucocorticoids on the viability and osteogenic differentiation of BMSCs. Transcriptome sequencing analysis revealed that the differentially expressed mRNAs regulated by SHED-derived exosomes were enriched mainly in signaling pathways such as the apoptosis pathway, the PI3K-Akt signaling pathway, the Hippo signaling pathway and the p53 signaling pathway. qPCR showed that SHED-derived exosomes reversed the dexamethasone-induced upregulation of HGF and ITGB8 expression and the inhibition of EFNA1 expression, but further increased the dexamethasone-induced downregulation of IL7 expression. In conclusion, SHED-derived exosomes partially reversed the inhibitory effects of glucocorticoids on BMSC proliferation and osteogenesis by inhibiting the expression of HGF, ITGB8 and IL7, and upregulating the expression of EFNA1.
PubMed: 38762017
DOI: 10.1016/j.gene.2024.148575 -
The Journal of Arthroplasty May 2024Periprosthetic knee fractures (PPKF) following total knee arthroplasty (TKA) are uncommon, but potentially serious injuries. We analyze the risk and risk factors for a...
BACKGROUND
Periprosthetic knee fractures (PPKF) following total knee arthroplasty (TKA) are uncommon, but potentially serious injuries. We analyze the risk and risk factors for a PPKF in standard primary TKA patients who have osteoarthritis (OA) and a minimally (cruciate-retaining TKAs without a femoral box cut) or posterior-stabilized TKA. In addition, we report the risk for patients who have other underlying knee disorders and/or a higher level of TKA constraint.
METHODS
All primary TKAs were identified from the Danish National Patient Register and the Danish Knee Arthroplasty Register using data between 1997 and 2022. Subsequent fractures were identified through the International Classifications of Disease (ICD) diagnosis code, Nordic Medico-Statistical Committee (NOMESCO) procedure code, or indication for revision TKA.
RESULTS
We included 120,642 standard primary TKA patients who had 1,434 PPKFs. The cumulated proportions were 0.3% (95% confidence interval (CI) 0.3 to 0.3) at 2 years 0.7% (0.6 to 0.7) at 5 years. At 10 years, the cumulated proportion was 1.5% (1.4 to 1.6), with 1.2% in the femur, 0.2% in the patella, and 0.1% in the tibia. Significant risk factors were (hazard ratio (HR) (95% CI)); ipsilateral hip arthroplasty (2.5 (2.1 to 2.8)); women (2.0 (1.8 to 2.3)), osteoporosis (1.4 (1.1 to 1.7)); age 80+ (1.4 (1.2 to 1.6)), and Charlson Comorbidity Index (CCI) score 3+ (1.4 (1.0 to 1.8)). An additional 22,624 primary TKA patients who had other underlying knee disorders and/or a higher level of implant constraint were included with 485 PPKFs. The 10-year cumulated proportions were 5.5% (95% CI 4.4 to 6.9) when the underlying disorder was a previous fracture, 2.3% (1.7 to 2.9) for rheumatic disorders, and 3.5% (1.4 to 8.8) for osteonecrosis. In patients who had condylar constrained knees, it was 4.3% (2.9 to 6.3), and 7.3% (4.1 to 13.1) for hinges.
CONCLUSION
In standard primary TKA patients, the 10-year cumulated proportion of PPKFs was 1.5%, and ipsilateral hip arthroplasty, women, osteoporosis, advanced age, and higher CCI increased the risk. Higher risks were observed in non-OA patients and/or patients who had a higher level of TKA constraint.
PubMed: 38759816
DOI: 10.1016/j.arth.2024.05.033 -
Archives of Medical Science : AMS 2024Hyperbaric oxygen (HBO) therapy involves the inhalation of pure oxygen in a pressure chamber under increased ambient pressure. Recent research indicates that circulating...
INTRODUCTION
Hyperbaric oxygen (HBO) therapy involves the inhalation of pure oxygen in a pressure chamber under increased ambient pressure. Recent research indicates that circulating small extracellular vesicles (sEVs) play important roles in human physiology and pathology. Therefore, the objective of this pilot study was to monitor the impact of HBO therapy on the levels of circulating sEVs in the serum of patients with necrotizing soft-tissue infections (NSTI), aseptic bone necrosis (ABN) or idiopathic sudden sensory neural hearing loss (ISSNHL).
MATERIAL AND METHODS
Serum-derived sEVs were isolated and quantified in 80 patients before and after HBO therapy applied for NSTI, ISSNHL and ABN patients as well as in normal controls who received neither HBO therapy nor steroids.
RESULTS
We observed a significant increase of circulating sEVs in patients with ISSNHL after HBO therapy ( < 0.05), as well as significantly elevated levels of sEVs after HBO therapy compared to patients with NSTI ( < 0.05) and ABN ( < 0.01).
CONCLUSIONS
The increase in the levels of sEVs in ISSNHL may be evidence for both the intended reduction of inflammation as a result of steroid therapy and the inhibitory effect of oxidative stress induced by HBO therapy. Thus, sEVs released during HBO therapy might play an important biological role in mediating the response to therapy and might be a promising approach to gain further insights into the therapeutic efficacy of HBO therapy.
PubMed: 38757025
DOI: 10.5114/aoms/169382 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Feb 2024Bone morphogenetic protein-4 (BMP4) has been proved to be an important regulatory factor for the pathological process of atherosclerosis (AS). However, there are few...
OBJECTIVES
Bone morphogenetic protein-4 (BMP4) has been proved to be an important regulatory factor for the pathological process of atherosclerosis (AS). However, there are few related clinical studies. This study aims to investigate the levels of plasma BMP4 in patients suffering from the arterial occlusive diseases (ACD) characterized by AS, and further to test the relationship between BMP4 and inflammation and vascular injury.
METHODS
A total of 38 ACD patients (the ACD group) and 38 healthy people for the physical examination (the control group) were enrolled. The plasma in each subject from both groups was obtained to test the levels of BMP4, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-10, and vascular endothelial cadherin (VE-cadherin), and the relationship between BMP4 and the detected indicators above were further analyzed.
RESULTS
Compared with the control group, the patients in the ACD group displayed significant elevations in the neutrophil to lymphocyte ratio [NLR, 1.63 (1.26, 1.91) vs 3.43 (2.16, 6.61)] and platelet to lymphocyte ratio [PLR, 6.37 (5.26, 7.74) vs 15.79 (7.97, 20.53)], while decrease in the lymphocyte to monocyte ratio [LMR, 5.67 (4.41, 7.14) vs 3.43 (2.07, 3.74)] (all <0.05). Besides, the ACD patients displayed significant elevations in plasma BMP4 [581.26 (389.85, 735.64) pg/mL vs 653.97(510.95, 890.43) pg/mL], TNF-α [254.16 (182.96, 340.70) pg/mL vs 293.29(238.90, 383.44) pg/mL], and VE-cadherin [1.54 (1.08, 2.13) ng/mL vs 1.85 (1.30, 2.54) ng/mL], and decrease in IL-10 [175.89 (118.39, 219.25) pg/mL vs 135.92 (95.80, 178.04) pg/mL] (all <0.05). While the levels of IL-1β remained statistically comparable between the 2 groups (=0.09). Furthermore, the plasma BMP4 levels were further revealed to be positively correlated with the levels of IL-1β (=0.35), TNF-α (=0.31) and VE-cadherin (=0.47), while they were negatively correlated with the levels of IL-10 (=-0.37; all <0.01).
CONCLUSIONS
After ACD occurrence, the patients' plasma concentrations of BMP4 would be upregulated, which may serve as a candidate to indicate the levels of inflammation and vascular injury.
Topics: Humans; Bone Morphogenetic Protein 4; Inflammation; Male; Female; Tumor Necrosis Factor-alpha; Arterial Occlusive Diseases; Interleukin-10; Interleukin-1beta; Cadherins; Case-Control Studies; Middle Aged; Antigens, CD; Vascular System Injuries; Neutrophils; Atherosclerosis; Aged; Adult; Lymphocytes
PubMed: 38755724
DOI: 10.11817/j.issn.1672-7347.2024.230264 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... May 2024To explore the feasibility and effectiveness of mixed reality technology for localizing perforator vessels in the repair of mandibular defects using free fibular flap.
OBJECTIVE
To explore the feasibility and effectiveness of mixed reality technology for localizing perforator vessels in the repair of mandibular defects using free fibular flap.
METHODS
Between June 2020 and June 2023, 12 patients with mandibular defects were repaired with free fibular flap. There were 8 males and 4 females, with an average age of 61 years (range, 35-78 years). There were 9 cases of ameloblastomas and 3 cases of squamous cell carcinomas involving the mandible. The disease duration ranged from 15 days to 2 years (median, 14.2 months). The length of mandibular defects ranged from 5 to 14 cm (mean, 8.5 cm). The area of soft tissue defects ranged from 5 cm×4 cm to 8 cm×6 cm. Preoperative enhanced CT scans of the maxillofacial region and CT angiography of the lower limbs were performed, and the data was used to create three-dimensional models of the mandible and lower limb perforator vessels. During operation, the mixed reality technology was used to overlay the three-dimensional model of perforator vessels onto the body surface for harvesting the free fibular flap. The length of the fibula harvested ranged from 6 to 15 cm, with a mean of 9.5 cm; the size of the flap ranged from 6 cm×5 cm to 10 cm×8 cm. The donor sites were sutured directly in 7 cases and repaired with free skin grafting in 5 cases.
RESULTS
Thirty perforator vessels were located by mixed reality technology before operation, with an average of 2.5 vessels per case; the distance between the exit point of the perforator vessels located before operation and the actual exit point ranged from 1 to 4 mm, with a mean of 2.8 mm. All fibular flaps survived; 1 case had necrosis at the distal end of flap, which healed after dressing changes. One donor site had infection, which healed after anti-inflammatory dressing changes; the remaining incisions healed by first intention, and the grafts survived smoothly. All patients were followed up 8-36 months (median, 21 months). The repaired facial appearance was satisfactory, with no flap swelling. Among the patients underwent postoperative radiotherapy, 2 patients had normal bone healing and 1 had delayed healing at 6 months.
CONCLUSION
In free fibular flap reconstruction of mandibular defects, the use of mixed reality technology for perforator vessel localization can achieve three-dimensional visualization, simplify surgical procedures, and reduce errors.
Topics: Humans; Male; Middle Aged; Female; Adult; Free Tissue Flaps; Aged; Fibula; Mandible; Plastic Surgery Procedures; Carcinoma, Squamous Cell; Mandibular Neoplasms; Mandibular Reconstruction; Perforator Flap; Ameloblastoma
PubMed: 38752246
DOI: 10.7507/1002-1892.202402027 -
Orthopedic Reviews 2024INTRODUCTION The incidence of periprosthetic fractures (PFFs) is estimated to range from 0.1% to 4.1%1, due to the increasing prevalence of joint arthroplasties, coupled...
INTRODUCTION The incidence of periprosthetic fractures (PFFs) is estimated to range from 0.1% to 4.1%1, due to the increasing prevalence of joint arthroplasties, coupled with an aging population. Numerous risk factors, including advanced age (>80 years), female gender, implant type, prior diagnoses of osteonecrosis and rheumatoid arthritis, revision surgery, aseptic stem mobilization, and the use of non-cemented stems, have been identified. Survivors of periprosthetic fractures often experience functional deterioration, facing a fourfold higher risk of hospitalization for postoperative complications compared to patients undergoing primary implantation, especially in the first postoperative year. MATERIALS AND METHODS Between 2018 and 2022, at the Maggiore Hospitals in Bologna and the San Matteo Policlinic in Pavia, we performed osteosynthesis on 84 patients with periprosthetic fractures of Vancouver type B1 or C. In 38 patients, we employed angular stable plates with the Zimmer Biomet NCB-PP® system. In 46 patients, we utilized INTRAUMA plates: DF distal femur and PFF proximal. Relevant postoperative follow-up outcomes considered included reintervention, infectious complications, radiographic healing, and functional recovery, with reference to changes in the Glasgow Outcome Scale (GOS) and the Harris Hip Score (HHS). All patients underwent clinical and radiographic evaluations during the follow-up period, averaging 28 months (range: 12-48 months), with a minimum follow-up duration of 12 months. RESULTS At the 4-month postoperative assessment, 71% of patients maintained their preoperative functional level, 19% experienced a 1-point GOS scale drop, and 10% died (GOS 5). The average HHS at 4 months was 80.2 points (range: 65-90). At the 6-month follow-up, 98.2% of patients achieved complete healing on radiographic examination. Only 1 patient (1.2%) developed a pseudoarthrosis site with synthesis device rupture. Only 1 patient (1.2%) required additional surgical treatment 2 years later due to the development of un aseptic perisynthetic fluid collection, while the remaining 5 patients (6%) who developed complications benefited from conservative treatment: 4 patients (3.6%) with infectious complications were treated with intravenous antibiotics. In the 2 patients (2.3%) with mobilization or rupture of synthesis devices, clinical and radiographic monitoring was opted for. 8 patients (10.7%) died: one 48 hours after the surgery, and the other 7 more than one month after the surgery. CONCLUSION Our clinical findings align with to existing scientific literature on periprosthetic fractures (B1 and C according to Vancouver classification). Moreover, good stability has been guaranteed at the radiological follow up by Zimmer Biomet NCB-PP® and INTRAUMA DF distal femur and PFF proximal plates. The locking construct allows for improved stability especially in osteoporotic bone.
PubMed: 38751453
DOI: 10.52965/001c.117203 -
Orthopaedic Surgery May 2024It is unclear whether less acetabular coverage is associated with the failure of core decompression (CD) for osteonecrosis of the femoral head (ONFH). This study aimed...
OBJECTIVE
It is unclear whether less acetabular coverage is associated with the failure of core decompression (CD) for osteonecrosis of the femoral head (ONFH). This study aimed to investigate the clinical outcomes of CD for ONFH with small- or medium-sized pre-collapse lesions, and determine what factors, especially acetabular anatomical parameters, predict the failure of CD.
METHODS
Between January 2010 and December 2022, we retrospectively reviewed 269 consecutive CDs in 188 patients diagnosed with ONFH with small- or medium-sized pre-collapse lesions. The Kaplan-Meier method was used to evaluate the survival rate of CD for ONFH with progression of collapse or conversion to total hip arthroplasty (THA) as the endpoint. Univariate and multivariate logistic regression analyses were conducted to identify the potential risk factors for the failure of CD. Receiver operating characteristic (ROC) curve analysis was further performed with conversion to THA as the endpoint to determine the predictive value of these factors.
RESULTS
The overall 5-year survival rate of CD for ONFH with small- or medium-sized pre-collapse lesions was 74.3% (95% confidence interval (CI) 69.0%-81.1%) with progression of collapse as the endpoint and 83.9% (95% CI 79.3%-88.7%) with conversion to THA as the endpoint. Univariate logistic regression analysis showed that bilateral affected hips was significantly associated with progression of collapse, and center-edge angle (CEA), sharp angle, acetabular head index (AHI), as well as acetabular depth ratio (ADR) were significantly associated with both progression of collapse and conversion to THA. Multivariate logistic regression analysis further indicated that CEA and AHI were independent risk factors for both progression of collapse and conversion to THA. ROC curve analysis with conversion to THA as the endpoint revealed that the cutoff values for CEA and AHI were 26.8° (sensitivity = 74.4%, specificity = 78.6%, area under the curve (AUC) = 0.809) and 79.8 (sensitivity = 78.4%, specificity = 73.8%, AUC = 0.818), respectively.
CONCLUSIONS
CD showed satisfactory clinical outcomes for ONFH with small- or medium-sized pre-collapse lesions where less acetabular coverage with a CEA < 26.8° or AHI < 79.8 was identified as an independent risk factor for the failure of CD.
PubMed: 38751150
DOI: 10.1111/os.14094 -
Frontiers in Endocrinology 2024Previous studies have reported that the occurrence and development of osteonecrosis is closely associated with immune-inflammatory responses. Mendelian randomization was...
BACKGROUND
Previous studies have reported that the occurrence and development of osteonecrosis is closely associated with immune-inflammatory responses. Mendelian randomization was performed to further assess the causal correlation between 41 inflammatory cytokines and osteonecrosis.
METHODS
Two-sample Mendelian randomization utilized genetic variants for osteonecrosis from a large genome-wide association study (GWAS) with 606 cases and 209,575 controls of European ancestry. Another analysis included drug-induced osteonecrosis with 101 cases and 218,691 controls of European ancestry. Inflammatory cytokines were sourced from a GWAS abstract involving 8,293 healthy participants. The causal relationship between exposure and outcome was primarily explored using an inverse variance weighting approach. Multiple sensitivity analyses, including MR-Egger, weighted median, simple model, weighted model, and MR-PRESSO, were concurrently applied to bolster the final results.
RESULTS
The results showed that bFGF, IL-2 and IL2-RA were clinically causally associated with the risk of osteonecrosis (OR=1.942, 95% CI=1.13-3.35, p=0.017; OR=0.688, 95% CI=0.50-0.94, p=0.021; OR=1.386, 95% CI=1.04-1.85, p = 0.026). there was a causal relationship between SCF and drug-related osteonecrosis (OR=3.356, 95% CI=1.09-10.30, p=0.034).
CONCLUSION
This pioneering Mendelian randomization study is the first to explore the causal link between osteonecrosis and 41 inflammatory cytokines. It conclusively establishes a causal association between osteonecrosis and bFGF, IL-2, and IL-2RA. These findings offer valuable insights into osteonecrosis pathogenesis, paving the way for effective clinical management. The study suggests bFGF, IL-2, and IL-2RA as potential therapeutic targets for osteonecrosis treatment.
Topics: Humans; Osteonecrosis; Mendelian Randomization Analysis; Genome-Wide Association Study; Cytokines; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Interleukin-2; Fibroblast Growth Factor 2; Inflammation
PubMed: 38745949
DOI: 10.3389/fendo.2024.1344917 -
Molecular Therapy. Oncology Jun 2024Chondrosarcoma (CS) is a malignant cartilage-forming bone tumor that is inherently resistant to chemotherapy and radiotherapy, leaving surgery as the only treatment...
Chondrosarcoma (CS) is a malignant cartilage-forming bone tumor that is inherently resistant to chemotherapy and radiotherapy, leaving surgery as the only treatment option. We have designed a tumor-targeted bacteriophage (phage)-derived particle (PDP), for targeted systemic delivery of cytokine-encoding transgenes to solid tumors. Phage has no intrinsic tropism for mammalian cells; therefore, it was engineered to display a double cyclic RGD4C ligand on the capsid to target tumors. To induce cancer cell death, we constructed a transgene cassette expressing a secreted form of the cytokine tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). We detected high expression of αvβ3 and αvβ5 integrin receptors of the RGD4C ligand, and of the TRAIL receptor-2 in human CS cells (SW1353), but not in primary normal chondrocytes. The RGD4C.PDP- particle carrying a luciferase reporter gene, , effectively and selectively mediated gene delivery to SW1353 cells, but not primary chondrocytes. Transduction of SW1353 cells with RGD4C.PDP encoding a human sTRAIL, resulted in the expression of TRAIL and subsequent cell death without harming the normal chondrocytes. Intravenous administration of RGD4C.PDP- to mice with established human CS resulted in a decrease in tumor size and tumor viability. Altogether, RGD4C.PDP- can be used to target systemic treatment of CS with the sTRAIL.
PubMed: 38745750
DOI: 10.1016/j.omton.2024.200805 -
Bone & Joint Open May 2024The localization of necrotic areas has been reported to impact the prognosis and treatment strategy for osteonecrosis of the femoral head (ONFH). Anteroposterior...
AIMS
The localization of necrotic areas has been reported to impact the prognosis and treatment strategy for osteonecrosis of the femoral head (ONFH). Anteroposterior localization of the necrotic area after a femoral neck fracture (FNF) has not been properly investigated. We hypothesize that the change of the weight loading direction on the femoral head due to residual posterior tilt caused by malunited FNF may affect the location of ONFH. We investigate the relationship between the posterior tilt angle (PTA) and anteroposterior localization of osteonecrosis using lateral hip radiographs.
METHODS
Patients aged younger than 55 years diagnosed with ONFH after FNF were retrospectively reviewed. Overall, 65 hips (38 males and 27 females; mean age 32.6 years (SD 12.2)) met the inclusion criteria. Patients with stage 1 or 4 ONFH, as per the Association Research Circulation Osseous classification, were excluded. The ratios of anterior and posterior viable areas and necrotic areas of the femoral head to the articular surface were calculated by setting the femoral head centre as the reference point. The PTA was measured using Palm's method. The association between the PTA and viable or necrotic areas of the femoral head was assessed using Spearman's rank correlation analysis (median PTA 6.0° (interquartile range 3 to 11.5)).
RESULTS
We identified a negative correlation between PTA and anterior viable areas (rho -0.477; p = 0.001), and no correlation between PTA and necrotic (rho 0.229; p = 0.067) or posterior viable areas (rho 0.204; p = 0.132).
CONCLUSION
Our results suggest that residual posterior tilt after FNF could affect the anteroposterior localization of necrosis.
PubMed: 38745542
DOI: 10.1302/2633-1462.55.BJO-2024-0051.R1