Mesenchymal stem cells-derived and siRNAs-encapsulated exosomes inhibit osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a progressive, obstinate and disabling disease. At present, the treatment of ONFH is still a global medical problem. We aim to explore the role of bone mesenchymal stem cells (BMSCs)-derived and siRNAs-encapsulated exosomes (siRNAs-encapsulated BMSCexos) in ONFH. We first isolated BMSCexos and screened siRNAs of 6 ONFH-related genes for siRNAs-encapsulated BMSCexo. The expression of these 6 ONFH-related genes in dexamethasone (DXM)-treated MC3T3-E1 cell, cell model of ONFH, was detected by RT-qPCR and Western blot analysis. And then, we performed CCK-8 assay, angiogenesis assay and HE staining analysis to test the promotion role of the siRNAs-encapsulated BMSCexo for angiogenesis during ONFH repair. The results suggest that the obtained particles were BMSCexos. The screened effective siRNAs could effectively knock down their expression in VECs. Moreover, siRNAs-encapsulated BMSCexo could effectively knock down the expression of these genes in VECs. In addition, siRNAs-encapsulated BMSCexo promote angiogenesis during ONFH repair. In conclusion, we found siRNAs-encapsulated BMSCexos could promote ONFH repair by angiogenesis, and indicated exosome as the new siRNA carrier is of great significance to improve the efficiency of RNAi.

Bifocal osteosynthesis to treat radial shortening deformity with dislocation of the inferior radioulnar joint.

BACKGROUND: Several methods have been reported to correct deformity and shortening of the distal radius. However, the results are not entirely satisfactory. The results of bifocal osteosynthesis were retrospectively analyzed in this study. METHODS: Eight patients treated with bifocal osteosynthesis were evaluated retrospectively. Pre-operative and post-operative clinical and radiographic examinations were performed. Subjective symptoms and objective joint function were assessed. Radiographic data of the extent of radial lengthening and distal radial articular angle were collected. RESULTS: The mean follow-up period was 46 months (37-68 months). Satisfactory wrist appearance and radial lengthening was achieved in all patients. All patients were satisfied with the wrist appearance and willing to undergo the same treatment again. The range of motion (ROM) of the forearm and wrist was significantly improved. Pin-track infections occurred in two patients, for which they received wound care and oral antibiotics. Complications such as fixation device failure, tendon rupture, fracture of regenerated bone or nerve impairment did not occur. The duration of lengthening depended on the shortening of the radius. Delayed union in the docking site was observed in two patients and union was achieved after bone grafting. CONCLUSIONS: Bifocal osteosynthesis using the Ilizarov method provides a useful method for correction of radial shortening deformity with dislocation of the inferior radioulnar joint. Despite the fact that we did not validate pre-and post-operation functional outcome scores, all patients were satisfied with the wrist appearance and function.

Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head.

BACKGROUND/AIMS: Osteonecrosis of the femoral head (ONFH) is a devastating orthopedic disease. Previous studies suggested that stromal-cell-derived factor (SDF)-1 was involved in osteogenesis and angiogenesis. However, whether SDF-1 potentiates the angiogenesis and osteogenesis of bone marrow-derived stromal stem cells (BMSCs) in ONFH is not clear. METHODS: BMSCs were transfected with green fluorescent protein (GFP) or the fusion gene encoding GFP and SDF-1α, and transgenic efficacy was monitored by immunofluorescence. The expression of SDF-1α, runt-related transcription factor 2 (Runx2, osteocalcin (OCN), and alkaline phosphatase (ALP) at the mRNA level was measured by real-time polymerase chain reactions (RT-PCR). The expression of SDF-1α, Runx2, OCN, and p-Smad1/5 were measured at the protein level by Western blot. Transwell migration assay and tube formation assay were utilized to detect the angiogenesis in vitro, whereas the in vivo angiogenesis was monitored by angiography. Immunohistological staining and micro-CT scanning were conducted to assess the histological changes in morphology. RESULTS: In vitro, SDF-1α overexpression in BMSCs promoted osteogenic differentiation and upregulated the expression of osteogenic-related proteins, such as ALP, Runx2, OCN, and p-Smadl/5. In the methylprednisolone induced ONFH rat model used in our investigation, the overexpression of SDF-1α in BMSCs promoted significantly more bone regeneration and the expression of OCN and Runx2 as compared with the effect of vehicle overexpression. Moreover, the morphology of ONFH was ameliorated after the transplantation of BMSCs with SDF-1α overexpression. Furthermore, SDF-1α overexpression in BMSCs significantly increased osteoblastic angiogenesis as indicated by the increased tube formation ability, CD31 expression, and vessel volume. CONCLUSION: SDF-1α overexpression in BMSCs promotes bone generation as indicated by osteogenesis and angiogenesis, suggesting SDF-1α may serve as a therapeutic drug target for ONFH treatment.

Relationship between the Apolipoprotein AI, B gene polymorphism and the risk of non-traumatic osteonecrosis.

BACKGROUND: Previous studies suggested that Apolipoprotein AI (ApoAI) and apolipoprotein B (ApoB) gene polymorphisms may result in lipid metabolism disorders. Genetic polymorphisms in these genes may be associated with the occurrence of osteonecrosis. METHODS: We designed a case-control study including 429 patients of osteonecrosis and 368 age- and sex-matched control subjects. Polymerase chain reaction was used to amplify the DNA fragments in promoter -75 G > A of ApoAI gene and EcoR I, Xba I and 3'-VNTR of ApoB gene in osteonecrosis patients and healthy controls. We utilized polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to genotype these four single nucleotide polymorphisms (SNPs). RESULTS: For -75 G > A polymorphism of ApoAI, AA genotype frequency (0.501) was significantly higher in patients with osteonecrosis than that in control (0.462) subjects (P <0.001), GA genotype frequency (0.170) was significantly lower than that in the control (0.310) group (P <0.0001). In osteonecrosis patients, the odds ratio (OR) of A allele was 3.932 (95% CI: 3.0847 ~ 5.0123), which suggested that subjects carrying A allele of promoter region -75 G > A of ApoAI gene had higher susceptibility to osteonecrosis than G allele carriers. The genotype and allele frequency distributions showed no significant difference in EcoR I, Xba Iand 3'-VNTR loci of ApoB gene between the osteonecrosis group and control group. CONCLUSION: Our study suggested that ApoAI gene -75G > A polymorphism may be associated with susceptibility to osteonecrosis in Chinese population. However, our results need further investigation with large sample size and various populations.

Identification and validation of SLCO4C1 as a biological marker in hepatocellular carcinoma based on anoikis classification features.

BACKGROUND: Hepatocellular carcinoma (HCC) exhibits a high degree of invasiveness and is closely associated with rapid disease progression. Multiple lines of evidence indicate a strong correlation between anoikis resistance and tumor progression, invasion, and metastasis. Nevertheless, the classification of anoikis in HCC and the investigation of novel biological target mechanisms in this context continue to pose challenges, requiring further exploration. METHODS: Combined with HCC samples from TCGA, GEO and ICGC databases, cluster analysis was conducted on anoikis genes, revealing novel patterns among different subtypes. Significant gene analysis of different gene subtypes was performed using WCGNA. The anoikis prognostic risk model was established by Lasso-Cox. Go, KEGG, and GSEA were applied to investigate pathway enrichment primarily observed in risk groups. We compared the disparities in immune infiltration, TMB, tumor microenvironment (TME), and drug sensitivity between the two risk groups. RT-qPCR and Western blotting were performed to validate the expression levels of SLCO4C1 in HCC. The biological functions of SLCO4C1 in HCC cells were assessed through various experiments, including CCK8 assay, colony formation assay, invasion migration assay, wound healing assay, and flow cytometry analysis. RESULTS: HCC was divided into 2 anoikis subtypes, and the subtypeB had a better prognosis. An anoikis prognostic model based on 12 (COPZ2, ACTG2, IFI27, SPP1, EPO, SLCO4C1, RAB26, STC2, RAC3, NQO1, MYCN, HSPA1B) risk genes is important for survival and prognosis. Significant differences were observed in immune cell infiltration, TME, and drug sensitivity analysis between the risk groups. SLCO4C1 was downregulated in HCC. SLCO4C1 downregulation promoted the proliferation, invasion, migration, and apoptosis of HCC cells. The tumor-suppressive role of SLCO4C1 in HCC has been confirmed. CONCLUSIONS: Our study presents a novel anoikis classification method for HCC that reveals the association between anoikis features and HCC. The anoikis feature is a critical biomarker bridging tumor cell death and tumor immunity. In this study, we provided the first evidence of SLCO4C1 functioning as a tumor suppressor in HCC.

Mitochondria from osteolineage cells regulate myeloid cell-mediated bone resorption.

Interactions between osteolineage cells and myeloid cells play important roles in maintaining skeletal homeostasis. Herein, we find that osteolineage cells transfer mitochondria to myeloid cells. Impairment of the transfer of mitochondria by deleting MIRO1 in osteolineage cells leads to increased myeloid cell commitment toward osteoclastic lineage cells and promotes bone resorption. In detail, impaired mitochondrial transfer from osteolineage cells alters glutathione metabolism and protects osteoclastic lineage cells from ferroptosis, thus promoting osteoclast activities. Furthermore, mitochondrial transfer from osteolineage cells to myeloid cells is involved in the regulation of glucocorticoid-induced osteoporosis, and glutathione depletion alleviates the progression of glucocorticoid-induced osteoporosis. These findings reveal an unappreciated mechanism underlying the interaction between osteolineage cells and myeloid cells to regulate skeletal metabolic homeostasis and provide insights into glucocorticoid-induced osteoporosis progression.

Edaravone, a novel free radical scavenger, prevents steroid-induced osteonecrosis in rabbits.

OBJECTIVE: To investigate the efficacy of edaravone, a novel free radical scavenger, on preventing steroid-induced osteonecrosis (ON) in a rabbit model. METHODS: Thirty-six New Zealand white rabbits were divided into control (C; n = 6), steroid-administered (S; n = 15) and edaravone-administered groups (E; n = 15) after receiving an established protocol of steroid-induced ON. Before and after steroid administration, plasma levels of reduced glutathione (GSH) and lipid peroxidation (LPO) were measured for oxidative stress. Two weeks later bilateral proximal femurs were dissected for micro-CT-based micro-angiography, and the presence or absence of ON and intravascular thrombi were examined histopathologically. Immunohistochemical examination of oxidative injury in bone tissue was conducted using the anti-8-hydoxy-2'-deoxyguanosine and anti-malondialdehyde mAbs. RESULTS: The incidence of ON in the E group (20%) was significantly lower than in the S group (73%). Three to five days after steroid administration, the plasma GSH level was significantly higher and LPO level was significantly lower in the E group than the S group. Compared with the S group, there were significantly more small-sized perfusion vessels and fewer large-sized dilated vessels in the E group. Thrombosis incidence was significantly lower in the E group than the S group. Intraosseous vessels and haematopoietic cells that sustained oxidative injury were significantly fewer in the E group than the S group. CONCLUSION: Edaravone exerted beneficial effects on reducing incidence of steroid-induced ON by suppressing the accumulation of lipid peroxidative products and oxidative DNA damage in endothelial cells and haematopoietic cells.

Disulfidptosis classification of hepatocellular carcinoma reveals correlation with clinical prognosis and immune profile.

A new mode of cell death, disulfidptosis, has been discovered. Clinical prognostic significance of disulfidptosis related pattern in hepatocellular carcinoma(HCC). In this study, a risk score model was established based on disulfidptosis model to analyze the role of risk score in clinical prognosis, immune cell infiltration, drug sensitivity and immunotherapy response. Disulfidptosis subtype were constructed based on the transcriptional profiles of 15 disulfidptosis-related genes(DRGs). All 601 samples were defined as high risk group(HRG) and low risk group(LRG) based on the disulfidptosis risk score. Drug sensitivity and response to immunotherapy were calculated by immunophenotypic score(IPS), tumor prediction, tumor immune dysfunction and rejection(TIDE). RT-qPCR was used to determine the mRNA level of disulfidptosis prognostic gene. Risk groups was identified as potential predictors of immune cell infiltration, drug sensitivity, and immunotherapy responsiveness. HRG may benefit from immunotherapy. Classification is very effective in predicting the prognosis and therapeutic effect of patients, and provides a reference for accurate individualized treatment. This study suggests that new biomarkers related to Disulfidptosis can be used in clinical diagnosis of liver cancer to predict prognosis and treatment targets.

Autologous Costal Cartilage Grafting for a Large Osteochondral Lesion of the Femoral Head: A 1-Year Single-Arm Study with 2 Additional Years of Follow-up.

BACKGROUND: There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients. METHODS: We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm 2 ) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping. RESULTS: All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up. CONCLUSIONS: ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Alleviation of synovitis caused by joint instability with application of platelet-rich plasma.

INTRODUCTION: Synovitis is an early set and persistent change during the progression of osteoarthritis, which causes symptoms such as pain and swelling of the joints. Platelet-rich plasma (PRP) can release quantities of growth factors and cytokines, and is proved effected in promoting restoration of multiple soft tissues. MATERIALS AND METHODS: In this study, twenty rabbits were used to establish animal model of synovitis, with the method of severing the anterior and posterior cruciate ligaments and removing the medial meniscus. Then the rabbits were evenly divided into the PRP group and the control group, and each group received injections of PRP and saline respectively once a week for 3 weeks consecutively, with the first injection administered 3 weeks postoperatively. RESULTS: The platelet count, the concentrations of growth factors in PRP and whole blood were investigated, and the IL-1ß concentration in the joint fluid was detected via ELISA. The synovium as well as the adjacent articular cartilage were collected for histological assessment. The platelet concentration in PRP is 6.8 fold of that in the whole blood. The IL-1ß level in the PRP group was lower than that in the control group 2 and 3 weeks after the administration of PRP. Histological investigation showed that the inflammatory reaction of the synovium and impact on the cartilage was much abated in the PRP group. CONCLUSIONS: PRP can effectively alleviate the synovitis caused by osteoarthritis following loss of joint stability. Given the autologous origin, its low cost and low risk features of PRP, it's a promising choice for OA patients to control the symptoms caused by synovitis.

Vascularized Fibular Grafting in Treatment of Femoral Neck Nonunion: A Prognostic Study Based on Long-Term Outcomes.

BACKGROUND: The purpose of this study was to evaluate the long-term efficacy and prognostic factors predicting success of revision surgery with free vascularized fibular grafting (FVFG) for treatment of femoral neck nonunion. METHODS: We prospectively enrolled patients who underwent revision surgery with FVFG between January 2001 and January 2013 in a tertiary hospital in China. A total of 98 patients with a minimum 5-year follow-up were included for analysis. The criteria for FVFG failure were conversion to hip arthroplasty, recommendation for a hip arthroplasty, or a Harris hip score of <80 points. Demographic information, the preoperative neck shortening ratio (NSR), the fixation method, and postoperative radiographic parameters including the postoperative NSR and neck-shaft angle (NSA) were recorded for prognostic analysis. RESULTS: At an average of 9.8 ± 3.5 years (range, 3 to 17 years) postoperatively, the overall success rate of this surgical procedure was 77% (75 of 98). The success and failure groups had no significant differences in age, fixation method, interval between initial fixation and revision surgery, or postoperative NSA. The success group had a significantly higher NSR than the failure group both preoperatively (77.8% versus 62.4%, p < 0.001) and postoperatively (87.6% versus 78.4%, p = 0.001). The receiver operating characteristic (ROC) curve analysis revealed an optimal cutoff for preoperative NSR of 60% to predict the outcome. Patients with a preoperative NSR of >60% had a success rate of 91% (68 of 75). CONCLUSIONS: Revision surgery with FVFG and internal fixation is an effective and important option for treating nonunion of the femoral neck in young patients without severe preoperative shortening and neck resorption (preoperative NSR of >60%). LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Platelet-rich plasma has beneficial effects in mice with osteonecrosis of the femoral head by promoting angiogenesis.

Platelet-rich plasma (PRP) is autologous and multifunctional. Platelet concentrate from blood contains highly concentrated platelets and various types of cells, including growth factors. PRP promotes the recovery of cell proliferation and differentiation. Osteonecrosis of the femoral head is a disease caused by femoral head damage or an insufficient blood supply, which leads to the death of bone cells and abnormal bone marrow composition. The subsequent repair of bone cells may result in changes to the structure of femoral head, femoral head collapse and joint dysfunction. PRP may promote the repair of injured articular cartilage in patients with joint diseases through the removal of harmful inflammatory factors. In the present study, the therapeutic effects and primary mechanism of PRP action were investigated using a glucocorticoid-induced femoral head osteonecrosis mouse model. Dexamethasone (DEX) and phosphate-buffered saline were used as controls. The therapeutic efficacy of PRP to treat osteonecrosis in murine femoral heads was evaluated by assessing clinical arthritis scores. The present study indicated that mice with osteonecrosis of the femoral head treated with PRP exhibited downregulated expression of interleukin (IL)-17A, IL-1ß, tumor necrosis factor-α, receptor activator of nuclear factor κ-B ligand, IL-6 and interferon-γ in the inflammatory tissue. In addition, the levels of hepatocyte growth factor, intercellular adhesion molecule-1, osteopontin, platelet-derived endothelial cell growth factor, vascular endothelial growth factor, platelet-derived growth factor, insulin-like growth factor-1 and transforming growth factor-ß were increased following treatment with PRP. Joint tissue histological staining demonstrated that PRP alleviated osteonecrosis of the femoral head and reduced humoral and cellular immune responses that promoted beneficial effects on the histological parameters. Furthermore, the concentration of glucocorticoids were significantly decreased in the serum of PRP-treated mice with osteonecrosis compared with the DEX group (P<0.01). Notably, PRP promoted beneficial effects in mice with osteonecrosis of the femoral head by stimulating angiogenesis. Therefore, the present study indicated that treatment with PRP promotes beneficial effects by preventing joint inflammation, cartilage destruction and bone damage, and stimulating the repair of joint tissue in mice with osteonecrosis of the femoral head. These preclinical data suggest that PRP may be developed as a novel method of treating osteonecrosis of the femoral head.

Downregulation of SOX3 leads to the inhibition of the proliferation, migration and invasion of osteosarcoma cells.

Sex determining region Y-box protein 3 (SOX3) is involved in embryonic development and tumorigenesis. However, the expression and precise role of SOX3 in osteosarcoma remain unclear. In this study, we reported that SOX3 expression was upregulated in osteosarcoma tissues compared with non-cancerous bone cyst tissues. To elucidate the cellular and molecular function of SOX3, we examined the consequences of SOX3 knockdown in osteosarcoma cells. We found that the downregulation of SOX3 inhibited the proliferation, migration and invasion of osteosarcoma cells. SOX3 downregulation also increased the cell population in the G1 phase and induced cell apoptosis. SOX3 knockdown-mediated cell cycle arrest and cell apoptosis were associated with decreased levels of Cdc25A, cyclin D1, proliferating cell nuclear antigen (PCNA) and Bcl-2, as well as an increased Bax expression. We also found that the downregulation of SOX3 decreased the expression of Snail, Twist and matrix metalloproteinase-9 (MMP-9), and increased E-cadherin expression, resulting in the inhibition of cell migration and invasion. Taken together, our data indicate that SOX3 may serve as an oncogene in osteosarcoma, and SOX3 downregulation may prove to be a novel approach for the inhibition of osteosarcoma progression.

Dimethyloxaloylglycine increases bone repair capacity of adipose-derived stem cells in the treatment of osteonecrosis of the femoral head.

Mesenchymal stem cells have been widely studied to promote local bone regeneration of osteonecrosis of the femoral head (ONFH). Previous studies observed that dimethyloxaloylglycine (DMOG) enhanced the angiogenic and osteogenic activity of mesenchymal stem cells by activating the expression of hypoxia inducible factor-1α (HIF-1α), thereby improving the bone repair capacity of mesenchymal stem cells. In the present study, it was investigated whether DMOG could increase the bone repair capacity of adipose-derived stem cells (ASCs) in the treatment of ONFH. Western blot analysis was performed to detect HIF-1α protein expression in ASCs treated with different concentrations of DMOG. The results showed DMOG enhanced HIF-1α expression in ASCs in a dose-dependent manner at least for 7 days. Furthermore, DMOG-treated ASCs were transplanted into the necrotic area of a rabbit model of ONFH to treat the disease. Four weeks later, micro-computed tomography (CT) quantitative analysis showed that 58.8±7.4% of the necrotic area was regenerated in the DMOG-treated ASCs transplantation group, 45.5±3.4% in normal ASCs transplantation group, 25.2±2.8% in only core decompression group and 10.6±2.6% in the untreated group. Histological analysis showed that transplantation of DMOG-treated ASCs clearly improved the bone regeneration of the necrotic area compared with the other three groups. Micro-CT and immunohistochemical analysis demonstrated the revasculation of the necrotic area were also increased significantly in the DMOG-treated ASC group compared with the control groups. Thus, it is hypothesized that DMOG could increase the bone repair capacity of ASCs through enhancing HIF-1α expression in the treatment of ONFH.

Efficacy of leukocyte- and platelet-rich plasma gel (L-PRP gel) in treating osteomyelitis in a rabbit model.

Leukocyte- and platelet-rich plasma gel (L-PRP gel), a new autologous product which was previously utilized in several surgical procedures to enhance tissue healing, is now increasingly used as a promising treatment method for infections. In this study, we investigated the antibacterial property of L-PRP gel against Methicillin-resistive Staphylococcus aureus (MRSA, ATCC 43300) in a rabbit model of osteomyelitis. Tibial osteomyelitis was induced in 40 New Zealand white rabbits using the MRSA strain. Three weeks after induction, the rabbits with tibial osteomyelitis were randomly divided into four groups: Control group (no treatment); Van group (debridement and parenteral treatment with vancomycin alone); L-PRP gel + Van group (debridement and local L-PRP gel injection, plus parenteral treatment with vancomycin); L-PRP gel group (debridement and local L-PRP gel injection). All rabbits were sacrificed 6 weeks after debridement. The antibacterial efficacy was evaluated by radiological, microbiological, and histological examinations. Newly formed bone was also quantified. The best therapeutic efficacy, including infection elimination and bone defect repair, was observed in the L-PRP gel + Van group. Although not comparable to vancomycin, L-PRP gel also exibited antimicrobial efficacy in vivo. We believe that a combination of L-PRP gel and antibiotics could be a favorable alternative for the treatment of osteomyelitis.

Diagnosis, management, and prevention of prosthetic joint infections.

As the number of joint prosthesis replacements worldwide increases exponentially, prosthetic joint infection (PJI), associated with prosthetic implants, has become a devastating complication associated with high morbidity and substantial cost. Patients who develop PJIs typically require extended hospitalization, additional surgical procedures, and long courses of parenteral antimicrobials. Defining the diagnostic criteria is complicated by patient heterogeneity. No single routinely used clinical test has been shown to achieve the ideal sensitivity, specificity, and accuracy for the diagnosis of PJI. Goals of treatment are to eradicate infection, prevent recurrence, and preserve mechanical joint function. Meanwhile, preventive strategies should be used in a timely and appropriate fashion. The present review will discuss the diagnosis, management, and prevention of PJI.

HIF-1α transgenic bone marrow cells can promote tissue repair in cases of corticosteroid-induced osteonecrosis of the femoral head in rabbits.

Although corticosteroid-induced osteonecrosis of the femoral head (ONFH) is common, the treatment for it remains limited and largely ineffective. We examined whether implantation of hypoxia inducible factor-1α (HIF-1α) transgenic bone marrow cells (BMCs) can promote the repair of the necrotic area of corticosteroid-induced ONFH. In this study, we confirmed that HIF-1α gene transfection could enhance mRNA expression of osteogenic genes in BMCs in vitro. Alkaline phosphatase activity assay and alizarin red-S staining indicated HIF-1α transgenic BMCs had enhanced osteogenic differentiation capacity in vitro. Furthermore, enzyme linked immunosorbent assay (ELISA) for VEGF revealed HIF-1α transgenic BMCs secreted more VEGF as compared to normal BMCs. An experimental rabbit model of early-stage corticosteroid-induced ONFH was established and used for an evaluation of cytotherapy. Transplantation of HIF-1α transgenic BMCs dramatically improved the bone regeneration of the necrotic area of the femoral head. The number and volume of blood vessel were significantly increased in the necrotic area of the femoral head compared to the control groups. These results support HIF-1α transgenic BMCs have enhanced osteogenic and angiogenic activity in vitro and in vivo. Transplantation of HIF-1α transgenic BMCs can potentially promote the repair of the necrotic area of corticosteroid-induced ONFH.

Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes.

Osteoarthritis (OA) is a major cause of disability in the adult population. As a progressive degenerative joint disorder, OA is characterized by cartilage damage, changes in the subchondral bone, osteophyte formation, muscle weakness, and inflammation of the synovium tissue and tendon. Although OA has long been viewed as a primary disorder of articular cartilage, subchondral bone is attracting increasing attention. It is commonly reported to play a vital role in the pathogenesis of OA. Subchondral bone sclerosis, together with progressive cartilage degradation, is widely considered as a hallmark of OA. Despite the increase in bone volume fraction, subchondral bone is hypomineralized, due to abnormal bone remodeling. Some histopathological changes in the subchondral bone have also been detected, including microdamage, bone marrow edema-like lesions and bone cysts. This review summarizes basic features of the osteochondral junction, which comprises subchondral bone and articular cartilage. Importantly, we discuss risk factors influencing subchondral bone integrity. We also focus on the microarchitectural and histopathological changes of subchondral bone in OA, and provide an overview of their potential contribution to the progression of OA. A hypothetical model for the pathogenesis of OA is proposed.