Three Birds, One Stone: An Osteo-Microenvironment Stage-Regulative Scaffold for Bone Defect Repair through Modulating Early Osteo-Immunomodulation, Middle Neovascularization, and Later Osteogenesis.

In order to repair critical-sized bone defects, various polylactic acid-glycolic acid (PLGA)-based hybrid scaffolds are successfully developed as bone substitutes. However, the byproducts of these PLGA-based scaffolds are known to acidify the implanted site, inducing tiresome acidic inflammation. Moreover, these degradation productions cannot offer an osteo-friendly microenvironment at the implanted site, matching natural bone healing. Herein, inspired by bone microenvironment atlas of natural bone-healing process, an osteo-microenvironment stage-regulative scaffold (P80/D10/M10) is fabricated by incorporating self-developed decellularized bone matrix microparticles (DBM-MPs) and multifunctional magnesium hydroxide nanoparticles (MH-NPs) into PLGA with an optimized proportion using low-temperature rapid prototyping (LT-RP) 3D-printing technology. The cell experiments show that this P80/D10/M10 exhibits excellent properties in mechanics, biocompatibility, and biodegradability, meanwhile superior stimulations in osteo-immunomodulation, angiogenesis, and osteogenesis. Additionally, the animal experiments determined that this P80/D10/M10 can offer an osteo-friendly microenvironment in a stage-matched pattern for enhanced bone regeneration, namely, optimization of early inflammation, middle neovascularization, and later bone formation. Furthermore, transcriptomic analysis suggested that the in vivo performance of P80/D10/M10 on bone defect repair is mostly attributed to regulating artery development, bone development, and bone remodeling. Overall, this study reveals that the osteo-microenvironment stage-regulative scaffold provides a promising treatment for bone defect repair.

Metformin accelerates bone fracture healing by promoting type H vessel formation through inhibition of YAP1/TAZ expression.

Due to increasing morbidity worldwide, fractures are becoming an emerging public health concern. This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures. Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis. Here, we show that metformin accelerated fracture healing in both osteoporotic and normal mice. Moreover, metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing. Mechanistically, metformin increased the expression of HIF-1α, an important positive regulator of type H vessel formation, by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells (HMECs). The results of HIF-1α or YAP1/TAZ interference in hypoxia-cultured HMECs using siRNA further suggested that the enhancement of HIF-1α and its target genes by metformin is primarily through YAP1/TAZ inhibition. Finally, overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair. In summary, our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.

Causal associations of brain structure with bone mineral density: a large-scale genetic correlation study.

In this study, we aimed to investigate the causal associations of brain structure with bone mineral density (BMD). Based on the genome-wide association study (GWAS) summary statistics of 1 325 brain imaging-derived phenotypes (BIDPs) of brain structure from the UK Biobank and GWAS summary datasets of 5 BMD locations, including the total body, femoral neck, lumbar spine, forearm, and heel from the GEFOS Consortium, linkage disequilibrium score regression (LDSC) was conducted to determine the genetic correlations, and Mendelian randomization (MR) was then performed to explore the causal relationship between the BIDPs and BMD. Several sensitivity analyses were performed to verify the strength and stability of the present MR outcomes. To increase confidence in our findings, we also performed confirmatory MR between BIDPs and osteoporosis. LDSC revealed that 1.93% of BIDPs, with a false discovery rate (FDR) < 0.01, were genetically correlated with BMD. Additionally, we observed that 1.31% of BIDPs exhibited a significant causal relationship with BMD (FDR < 0.01) through MR. Both the LDSC and MR results demonstrated that the BIDPs "Volume of normalized brain," "Volume of gray matter in Left Inferior Frontal Gyrus, pars opercularis," "Volume of Estimated Total Intra Cranial" and "Volume-ratio of brain segmentation/estimated total intracranial" had strong associations with BMD. Interestingly, our results showed that more left BIDPs were causally associated with BMD, especially within and around the left frontal region. In conclusion, a part of the brain structure causally influences BMD, which may provide important perspectives for the prevention of osteoporosis and offer valuable insights for further research on the brain-bone axis.

Post-traumatic distal ulnar bifurcation in children: a case report.

BACKGROUND: Galeazzi fracture dislocation is a compound injury that encompasses fractures of the distal third of the radius and dislocation of the distal radial ulnar joint (DRUJ). Clinically, this condition is rare and often leads to distal ulnar bifurcation. In previous similar reports, patients were effectively managed through surgery. CASE PRESENTATION: In this case report, we describe an 11-year-old male child who presented with an ulnar bifida following trauma to the hand, and was treated with manipulation and conservative treatment without surgery. A follow-up performed over the years demonstrated that the patient recovered well, and had normal wrist movements without significant pain, and the patient expressed great satisfaction. CONCLUSIONS: Ulnar diaphyseal fracture may occur in children or adolescents due to injuries, and may be accompanied with manipulation and repositioning. Conservative treatment can be applied to avoid the trauma associated with surgery especially in the absence of severe joint mobility impairment with good outcomes.

Menstrual Blood-Derived Mesenchymal Stem Cells Encapsulated in Autologous Platelet-Rich Gel Facilitate Rotator Cuff Healing in a Rabbit Model of Chronic Tears.

BACKGROUND: Successful management of chronic rotator cuff (RC) tears remains a challenge owing to its limited intrinsic healing capacity and unsatisfactory failure rate. Menstrual blood-derived mesenchymal stem cells (MenSCs) have the potential to differentiate into the chondrogenic or osteogenic lineage. Autologous platelet-rich gel (APG), a gel material derived from platelet-rich plasma (PRP), can be applied as a carrier system for cell delivery and also as a releasing system for endogenous growth factors. PURPOSE: To investigate the effect of human MenSCs encapsulated in APG (MenSCs@APG) on the healing of chronic RC tears in a rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: After evaluation of the effect of PRP on MenSC proliferation or differentiation, the stem cells were encapsulated in APG for in vivo injection. Supraspinatus tenotomy from the right greater tuberosity was performed on 45 New Zealand White rabbits. After 6 weeks, these rabbits were randomly allocated to 3 supplemental treatments during supraspinatus repair: saline injection (control [CTL] group), APG injection (APG group), and MenSCs@APG injection (MenSCs@APG group). At week 18, these rabbits were sacrificed to harvest the humerus-supraspinatus tendon complexes for micro-computed tomography (CT), histological evaluation, tensile test, and MenSC tracking. RESULTS: In vitro results showed that APG can stimulate MenSC proliferation and enhance chondrogenic or osteogenic differentiation. In vivo results showed that APG can act as a carrier for delivering MenSCs into the healing site, and also as a stimulator for enhancing the in vivo performance of MenSCs. Micro-CT showed that bone volume/total volume and trabecular thickness of the new bone in the MenSCs@APG group presented significantly larger values than those of the APG or CTL group (P < .05 for all). Histologically, compared with the CTL or APG group, significantly more mature fibrocartilage regenerated at the healing site in the MenSCs@APG group. A large number of human nuclei-stained cells were observed in the MenSCs@APG group, presenting a similar appearance to fibrochondrocytes or osteocytes. Biomechanically, the MenSCs@APG group showed significantly higher failure load and stiffness than the APG or CTL group (P < .05 for all). CONCLUSION: Human MenSCs@APG facilitated RC healing in a rabbit model of chronic tears. CLINICAL RELEVANCE: Autogenous MenSCs@APG may be a new stem cell-based therapy for augmenting RC healing in the clinic.

Analysis of high-risk factors for preoperative DVT in elderly patients with simple hip fractures and construction of a nomogram prediction model.

BACKGROUND: Hip fractures are anatomically classified in relation to femoral neck, intertrochanteric or subtrochanteric fractures. Simple hip fractures discussed in this study are femoral neck fractures or intertrochanteric fractures, which are the most common types of hip fractures. Controversy remains regarding the value of biochemical indices of thrombosis in elderly patients with fractures. A retrospective study was conducted to investigate the index admission data in blood draws of elderly patients with hip fractures and their high-risk factors for deep venous thrombosis (DVT). A nomogram prediction model for DVT was established to facilitate a rapid, accurate, and effective prediction based on the results. METHODS: The data were based on 562 elderly patients undergoing hip fracture surgery, from whom 274 patients were selected for enrollment. The 274 patients were divided into two groups using preoperative vascular color Doppler ultrasonography. Chi-square tests, t-tests, and U tests were conducted, and logistic regression analysis was conducted showing different factors between the two groups. Independent risk factors with statistical significance (P < 0.05) were obtained, and the logistic regression equation and the new variable prediction probability_1 (PRE_1) were constructed. The receiver operating characteristic (ROC) curve of risk factors and PRE_1 was drawn to obtain the area under the curve (AUC) and truncation value of each risk factor. Finally, a nomogram prediction model was constructed using the R programming language to calculate the concordance index (C-index). RESULTS: Time from injury to hospitalization, platelet (PLT) count, D-dimer level, fibrinogen (FIB) level, and systemic immune-inflammatory index (SII) score were independent risk factors for preoperative DVT in elderly patients with hip fractures. The logistic regression equation and PRE_1 were constructed by combining the above factors. ROC analysis showed that the area under the curve for PRE_1 (AUC = 0.808) was greater than that of the other factors. The sensitivity of PRE_1 (sensitivity = 0.756) was also higher than that of the other factors, and the specificity of PRE_1 (specificity = 0.756) was higher than that of two other factors. Moreover, a predictive nomogram was established, and the results showed a high consistency between the actual probability and the predicted probability (C-index = 0.808), indicating a high predictive value in fractures accompanied by DVT. CONCLUSIONS: This study confirmed that SII score could be used as a risk factor in the prediction of DVT occurrence. A nomogram prediction model was constructed by combining 5 independent risk factors: time from injury to admission, PLT count, D-dimer level, FIB level, and SII score, which had high predictive values for fractures accompanied by DVT. This model use is limited to simple hip fracture.

Mg2+ -mediated autophagy-dependent polarization of macrophages mediates the osteogenesis of bone marrow stromal stem cells by interfering with macrophage-derived exosomes containing miR-381.

Magnesium ion (Mg2+ ) has received increased attention due to the roles it plays in promoting osteogenesis and preventing inflammation. This study was designed to investigate the mechanism by which Mg2+ influences the osteoblastic differentiation of bone marrow stromal stem cells (BMSCs). The polarization of Mø (macrophages) was measured after treatment with Mg2+ . Meanwhile, autophagy in Mø was measured by detecting LC3B expression. Mø-derived exosomes were isolated and cocultured with BMSCs; after which, osteogenic differentiation was evaluated by Alizarin Red staining and detection of alkaline phosphatase (ALP). Our results showed that Mg2+ could induce autophagy in macrophages and modulate the M1/M2 polarization of macrophages. Mg2+ -mediated macrophages could facilitate the osteogenic differentiation of BMSCs by regulating autophagy, and this facilitation by Mg2+ -mediated macrophages was closely related to macrophage-derived exosomes, and especially exosomes containing miR-381. However, miR-381 in macrophages did not influence autophagy or the polarization of Mg2+ -mediated macrophages. Furthermore, macrophage-derived exosomes containing miR-381 mainly determined the osteogenic differentiation of BMSCs. Mg2+ -mediated macrophages were shown to promote the osteogenic differentiation of BMSCs via autophagy through reducing miR-381 in macrophage-derived exosomes. In conclusion, our results suggest Mg2+ -mediated macrophage-derived exosomes containing miR-381 as novel vehicles for promoting the osteogenic differentiation of BMSCs.

Three-dimensional mapping of distal humerus fracture.

BACKGROUND: Distal humerus fractures (DHFs) constitute one-third of elbow fractures approximately. In this study, we aim to define and analyze the fracture lines and morphological features of DHFs using mapping technique. METHODS: One hundred and two DHFs were retrospectively reviewed. All the computed tomography (CT) data were used to manually reconstruct and virtually reduce the DHF fragments to fit a standard 3D model. Smooth curves were depicted accurately onto the surface of the template to represent the fracture lines. All the curves were overlapped onto the model to create the 3D fracture map and heat map. RESULTS: Our analysis was based on 102 CT images of DHFs, contributed by 59 male and 43 female patients (mean age, 46 years; range, 18-93 years), and included 15 type A, 25 type B, and 62 type C fractures. On mapping, the hot zones were located in the radial fossa, coronoid fossa, olecranon fossa, and the external part of the trochlear. Conversely, the cold zones were noted in medial condyle, the medial side of the trochlear, and the anterolateral area on the supracondylar ridge. CONCLUSIONS: Our study firstly shows the fracture lines and morphological features of distal humeral fractures by three-dimensional mapping technology. Distal humerus fracture lines are characteristic and highly related to the micro-architecture difference of distal humerus, which may provide some guidance for the treatment plan selection and surgical fixation design.

Mg(OH)2 nanoparticles enhance the antibacterial activities of macrophages by activating the reactive oxygen species.

Infection often causes disastrous consequences in all fields of clinical medicine, especially orthopedics. Hence, critical efforts are being made to engineer novel nanomaterials for the treatment of orthopedic infections due to the high biocompatibility and antibacterial properties they possess. The purpose of this study was to investigate the antibacterial effects of magnesium hydroxide (Mg(OH)2 ) nanoparticles (NPs) in vitro and determine their possible mechanisms of action. In this study, Escherichia coli was selected as the pathogenic bacteria and it was found that Mg(OH)2 NPs significantly inhibited the growth of E. coli by promoting nucleic acid leakage, inhibiting protein synthesis, and suppressing the metabolic activity. The minimum inhibitory concentration for these bacteria was determined to be 4.4 µg/ml. In vitro flow cytometry and immunofluorescence tests indicated that Mg(OH)2 NPs induced the macrophages to generate reactive oxygen species to kill the bacteria. To understand the mechanisms involved in this process, western blotting was performed and it was found that Mg(OH)2 NPs activated the phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/Akt) signaling pathway of macrophages to enhance their phagocytosis with no obvious cytotoxicity. Thus, Mg(OH)2 NPs are a suitable choice to develop promising agents or coating materials for the treatment of clinically widespread infections in view of their safety, biocompatibility, and powerful antibacterial properties.

Construction and efficiency analysis of prediction model for venous thromboembolism risk in the elderly after hip fracture. / è€å¹´é«‹éƒ¨éª¨æŠ˜åŽé™è„‰è¡€æ “æ “å¡žç—‡é£Žé™©é¢„æµ‹æ¨¡åž‹çš„æž„å»ºåŠé¢„æµ‹æ•ˆèƒ½.

OBJECTIVES: To screen the risk factors for predicting venous thromboembolism (VTE) risk after hip fracture in the elderly, to establish a prediction model based on these factors, and to analyze its prediction efficacy. METHODS: A total of 52 hip fracture patients over 60 years old with VTE admitted to the Department of Orthopaedic Trauma, Xiangya Hospital, Central South University from March 2017 to April 2019 were selected as a thrombus group, and another 52 hip fracture patients over 60 years old without VTE were selected as a control group. The differences of hospitalization data and examination results between the 2 groups were compared. Logistic regression model was used to explore the influence of risk factors on VTE risk after hip fracture in the elderly and construct the prediction model based on these factors. The receiver operating characteristic curve was used to analyze the predictive effectiveness of model, Hosmer-lemeshow goodness of fit test was used to evaluate the fitting degree of prediction model. RESULTS: Univariate analysis showed that injury-admission interval, Caprini score, WBC count, platelet count, neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammatory index (SII), and fibrinogen in the thrombus group were higher than those in the control group (all P<0.05). Logistic regression analysis showed that injury-admission interval, Caprini score, and SII were independent predictors of VTE risk after hip fracture in the elderly. The AUC was 0.949 (95% CI 0.901 to 0.996) when the sensitivity and specificity were 82.70% and 96.20%, respectively, which were significantly higher than each single index, and the prediction model had perfect fitting degree (Hosmer-lemeshow χ2=14.078, P>0.05). CONCLUSIONS: SII, Caprini score, and injury-admission interval are independent predictors of VTE after hip fracture in the elderly. The prediction model based on these 3 factors has a good efficacy on the prediction of VTE risk, and could provide important reference for the prevention, management, and treatment of VTE after hip fracture in the elderly.

DHCR7 rs12785878 T>C Polymorphism Is Associated With an Increased Risk of Early Onset of Alzheimer's Disease in Chinese Population.

Background: Vitamin D insufficiency has been considered a risk factor for Alzheimer's disease (AD) in several studies. Recently, four single-nucleotide polymorphisms (SNPs) to be genome-wide significant for 25-hydroxyvitamin D [25(OH)D] were identified to have an association with the risk of AD. These include GC rs2282679 A>C, CYP2R1 rs10741657 T>C, DHCR7 rs12785878 T>C, and CYP24A1 rs6013897 T>A. However, the association between these polymorphisms and AD susceptibility in the Chinese population remains unclear. Methods: A case-control cohort study was conducted in 676 AD patients (mean age at onset was 69.52 ± 10.90 years, male: 39.2%) and 551 healthy controls (mean age was 67.73 ± 6.02 years, male: 44.8%). Genotyping was determined by PCR and SNaPshot sequencing. To determine whether the four SNPs account for risks in AD in Chinese population, multivariate logistic regression models were performed. Stratified analysis was performed based on gender and age of onset of AD, separately. Statistical significance was set at 0.0125 (0.05/4) based on Bonferroni correction. Findings: DHCR7 rs12785878 T>C was found to be significantly associated with an increased risk of early-onset Alzheimer's disease (EOAD) (n = 300, risk allele C, adjusted OR = 1.542, adjusted 95% CI = 1.176-2.023, p = 0.002). There was no statistical significance of the other three SNPs between the two groups. Interpretation: Our results suggested that DHCR7 rs12785878 T>C might be associated with an increased risk of EOAD in the Chinese population, while other polymorphisms related to vitamin D insufficiency might not be. However, due to the limited data in this study, replication studies in a larger sample are required.

MicroRNA-130a controls bone marrow mesenchymal stem cell differentiation towards the osteoblastic and adipogenic fate.

OBJECTIVES: With age, bone marrow mesenchymal stem cells (BMSC) have reduced ability of differentiating into osteoblasts but have increased ability of differentiating into adipocytes which leads to age-related bone loss. MicroRNAs (miRNAs) play major roles in regulating BMSC differentiation. This paper explored the role of miRNAs in regulating BMSC differentiation swift fate in age-related osteoporosis. MATERIAL AND METHODS: Mice and human BMSC were isolated from bone marrow, whose miR-130a level was measured. The abilities of BMSC differentiate into osteoblast or fat cell under the transfected with agomiR-130a or antagomiR-130a were analysed by the level of ALP, osteocalcin, Runx2, osterix or peroxisome proliferator-activated receptorγ (PPARγ), Fabp4. Related mechanism was verified via qT-PCR, Western blotting (WB) and siRNA transfection. Animal phenotype intravenous injection with agomiR-130a or agomiR-NC was explored by Micro-CT, immunochemistry and calcein double-labelling. RESULTS: MiR-130a was dramatically decreased in BMSC of advanced subjects. Overexpression of miR-130a increased osteogenic differentiation of BMSC and attenuated adipogenic differentiation in BMSC, conversely, Inhibition of miR-130a reduced osteogenic differentiation and facilitated lipid droplet formation. Consistently, overexpression of miR-130a in elderly mice dropped off the bone loss. Furthermore, the protein levels of Smad regulatory factors 2 (Smurf2) and PPARγ were regulated by miR-130a with an negative effect through directly combining the 3'UTR of Smurf2 and PPARγ. CONCLUSIONS: The results indicated that miR-130a promotes osteoblastic differentiation of BMSC by negatively regulating Smurf2 expression and suppresses adipogenic differentiation of BMSC by targeting the PPARγ, and supply a new target for clinical therapy of age-related bone loss.

miR-381 modulates human bone mesenchymal stromal cells (BMSCs) osteogenesis via suppressing Wnt signaling pathway during atrophic nonunion development.

The osteogenic differentiation of human bone mesenchymal stromal cells (BMSCs) has been considered as a central issue in fracture healing. Wnt signaling could promote BMSC osteogenic differentiation through inhibiting PPARγ. During atrophic nonunion, Wnt signaling-related factors, WNT5A and FZD3 proteins, were significantly reduced, along with downregulation of Runx2, ALP, and Collagen I and upregulation of PPARγ. Here, we performed a microarray analysis to identify differentially expressed miRNAs in atrophic nonunion tissues that were associated with Wnt signaling through targeting related factors. Of upregulated miRNAs, miR-381 overexpression could significantly inhibit the osteogenic differentiation in primary human BMSCs while increase in PPARγ protein level. Through binding to the 3'UTR of WNT5A and FZD3, miR-381 modulated the osteogenic differentiation via regulating ß-catenin nucleus translocation. Moreover, PPARγ, an essential transcription factor inhibiting osteogenic differentiation, could bind to the promoter region of miR-381 to activate its expression. Taken together, PPARγ-induced miR-381 upregulation inhibits the osteogenic differentiation in human BMSCs through miR-381 downstream targets, WNT5A and FZD3, and ß-catenin nucleus translocation in Wnt signaling. The in vivo study also proved that inhibition of miR-381 promoted the fracture healing. Our finding may provide a novel direction for atrophic nonunion treatment.

Novel ATL1 mutation in a Chinese family with hereditary spastic paraplegia: A case report and review of literature.

BACKGROUND: Hereditary spastic paraplegias (HSPs) refer to a group of heterogeneous neurodegenerative diseases characterized by lower limbs spasticity and weakness. So far, over 72 genes have been found to cause HSP (SPG1-SPG72). Among autosomal dominant HSP patients, spastic paraplegia 4 (SPG4/SPAST) gene is the most common pathogenic gene, and atlastin-1 (ATL1) is the second most common one. Here we reported a novel ATL1 mutation in a Chinese spastic paraplegia 3A (SPG3A) family, which expands the clinical and genetic spectrum of ATL1 mutations. CASE SUMMARY: A 9-year-old boy with progressive spastic paraplegia accompanied by right hearing loss and mental retardation for five years was admitted to our hospital. Past history was unremarkable. The family history was positive, and his grandfather and mother had similar symptoms. Neurological examinations revealed hypermyotonia in his lower limbs, hyperreflexia in knee reflex, bilateral positive Babinski signs and scissors gait. The results of blood routine test, liver function test, blood glucose test, ceruloplasmin test and vitamin test were all normal. The serum lactic acid level was significantly increased. The testing for brainstem auditory evoked potential demonstrated that the right side hearing was impaired while the left was normal. Magnetic resonance imaging showed mild atrophy of the spinal cord. The gene panel test revealed that the proband carried an ATL1 c.752A>G p.Gln251Arg (p.Q251R) mutation, and Sanger sequencing confirmed the existence of family co-segregation. CONCLUSION: We reported a novel ATL1 Q251R mutation and a novel clinical phenotype of hearing loss in a Chinese SPG3A family.

Diagnosis and treatment of hyperextension bicondylar tibial plateau fractures.

PURPOSE: To report the diagnosis, injury mechanisms, and imaging characteristics of hyperextension bicondylar tibial plateau fractures and examine the indications and feasibility of the modified anterior midline incision as a treatment strategy. METHODS: We performed a retrospective analysis of 11 cases of hyperextension bicondylar tibial plateau fractures who were treated with open reduction and internal fixation, predominantly via an anterolateral and posteromedialdouble incision or a modified anterior midline incision. Radiological and functional evaluations were performed. RESULTS: Eleven patients were followed-up for a mean period of 11.5 months (range 3-24 months). The mean time to radiographic bony union was 12.5 weeks (range 10-26 weeks). At final follow-up, the average Rasmussen functional score was 26.8 (range 24 - 29); five patients had an excellent rating, and six a good rating. The average range of motion of the affected knees was 3.4-130° postoperatively. Fixation failure was not observed in any of the treated fractures. CONCLUSION: Hyperextension bicondylar tibial plateau fractures show a special Tiankeng-like collapse characteristic, while the changes in posterior tibial slope angle are easy to overlook. The modified anterior midline incision is a safe and effective approach for treatment of hyperextension bicondylar tibial plateau fractures with less rear displacement. Open reduction and double plating for the treatment of hyperextension bicondylar tibial plateau fractures provides excellent results.

MiR-19b-3p regulates osteogenic differentiation of PDGFRα+ muscle cells by specifically targeting PTEN.

Heterotopic ossification (HO) is a common disturbing complication of intra-articular fractures. Its prevention and treatment are still difficult as its pathogenesis is unclear. It was reported that PDGFRα+ muscle cells in skeletal muscle may participate in the formation of HO; however, the specific mechanism is still unknown. This study investigated the function of miR-19b-3p in osteogenic differentiation of PDGFRα+ muscle cells. MiR-19b-3p was upregulated during PDGFRα+ muscle cell osteogenic differentiation. The exogenous expression of miR-19b-3p led to an increase in osteogenic marker gene transcription and translation during the osteogenic differentiation of PDGFRα+ muscle cells. Furthermore, both alkaline phosphatase and alizarin red staining increased in miR-19b-3p mimic transfected cells. Over-expression of miR-19b-3p led to the down-regulation of gene of phosphate and tension homology deleted on chromosome ten (PTEN). Additionally, the dual luciferase reporter assay demonstrated that PTEN was a direct target of miR-19b-3p. The increase of osteocalcin, osteopontin, and Runt-related transcription factor 2 protein levels induced by ectopic miR-19b-3p expression could be partially reversed by PTEN over-expression. In conclusion, our results suggested that miR-19b-3p may be a promising target in inhibiting PDGFRα+ muscle cell osteogenic differentiation and treatment of HO.

The association between CD31hiEmcnhi endothelial cells and bone mineral density in Chinese women.

Osteoporosis is the most common bone disease in humans. During bone remodeling, specialized blood vessels influenced by the endothelial cells (CD31hiEmcnhi, also called type H cells) are formatted to supply nutrients. Reductions in vascular supply are associated with bone loss resulting in osteoporosis. Therefore, the objective of the present study was to explore the association between the CD31hiEmcnhi endothelial cells and bone mineral density (BMD). In this prospective study, 134 Chinese women were enrolled and examined. BMD was measured by DEXA method while the percentage of CD31hiEmcnhi endothelial cells in the intertrochanteric part was measured by flow cytometry. The percentage of CD31hiEmcnhi endothelial cells in postmenopausal subjects was significantly lower compared with premenopausal women (8.7 ± 4.0% vs 13.2 ± 5.6%, P < 0.01). Meanwhile, the CD31hiEmcnhi endothelial cell levels in osteopenia and osteoporosis were significantly lower compared with subjects with normal BMD (9.84 ± 4.2% in osteopenia and 7.11 ± 3.2% in osteoporosis vs 12.7 ± 5.6% in subjects with normal T score, P < 0.01). Multiple regression analyses showed that the CD31hiEmcnhi endothelial cells level was positively associated with femur neck and total hip BMD, but not with lumbar BMD. Our study suggests a significantly positive association between CD31hiEmcnhi endothelial cells and local BMD in Chinese women. The proportion of CD31hiEmcnhi endothelial cells is a marker of bone quality and represents a potential target for treatment of bone loss.

Evaluation of the mechanisms and effects of Mg-Ag-Y alloy on the tumor growth and metastasis of the MG63 osteosarcoma cell line.

Osteosarcoma is a malignant primary bone tumor, which often associates with pulmonary metastasis. The radical surgery of osteosarcoma often requires internal orthopedic implants. Therefore, implants with antitumor properties should be developed. Magnesium (Mg) and its alloys possess great potential as orthopedic materials, given their biodegradable properties, superior osteogenesis performance, and antitumor features. However, problems arise with their uncontrolled degradation rates and their unknown antitumor mechanisms. In our study, when compared with pure Mg, the rare element silver alloyed with yttrium (Ag-Y) could extremely enhance the corrosion resistance of these elements, giving the Ex-Mg-1Ag-1Y alloy better anticorrosion rates. Here, we implanted the Ex-Mg-1Ag-1Y alloy and pure Mg and Ti alloy in vivo around tumors in nude mice (BALB/c). Notably, the local tumor weight in Mg alloy and pure Mg groups were much smaller than that in Ti alloy group in 36 days after surgery (6.59 ± 0.70, 6.76 ± 0.62, and 8.54 ± 0.56 g), while the general scores of lung metastasis in Mg alloy and pure Mg groups were also lower than Ti alloy group (64.50 ± 7.64, 62.73 ± 7.84, and 87.60 ± 9.43). Therefore, the Mg and Ex-Mg-1Ag-1Y alloy, both demonstrated resisting effects against local tumor growth and pulmonary metastasis, which could be performed by changing the extracellular acidosis microenvironment, elevating the Mg concentration, suppressing C-X-C chemokine receptor type 4 (CXCR4) levels, and increasing prostacyclin (PGI2 ) synthesis. Our work revealed that the Ex-Mg-1Ag-1Y alloy may be a promising orthopedic implant for treating osteosarcoma due to its better corrosion resistance and antitumor attributes. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2537-2548, 2019.

Compression screws and buttress plate versus compression screws only for Hoffa fracture in Chinese patients: a comparative study.

OBJECTIVE: To compare compression screws and buttress plate (CS plus BP) with compression screws only (CS) in treating patients with Hoffa fracture. METHODS: This retrospective study included Chinese patients with Hoffa fracture treated by open reduction and internal fixation. Radiographs and clinical outcomes (range of movement [ROM], bone union and Knee Society Score [KSS]) were compared between patients treated using CS plus BP versus CS only. RESULTS: At 4 months following surgery, significantly better outcomes were shown in the CS plus BP group ( n = 24) versus CS only group ( n = 21) regarding ROM (120.4 ± 5.2° versus 110 ± 7.1°) and KSS (85.5 ± 4.1 versus 79.7 ± 3.3). At the 12-month follow-up, significantly better outcomes were maintained in the CS plus BP versus CS only group regarding ROM (126.2 ± 7.4° versus 120.5 ± 8.2°) and KSS (88.3 ± 4.6 versus 84.2 ± 4.0). At the final follow-up, all patients had normal fracture healing and no malunion, nonunion or reduction loss. CONCLUSIONS: Fixation with CS plus BP for Hoffa fracture is effective and reliable, and may provide more adequate stability and better outcomes versus CS only.