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To improve the bioperformances of porous polyetheretherketone (PPK) for bone repair, silicon nitride-coated PPK (CSNPPK) was prepared by a method of suspension coating and melt binding. The results revealed that, as compared with PPK, the surface roughness, compressive strength, and water absorption of CSNPPK increased, while the pore size and porosity of CSNPPK exhibited no obvious changes. In addition, the cellular responses (including attachment, proliferation, and differentiation as well as osteogenically related gene expressions) of the MC3T3-E1 cells to CSNPPK were remarkably promoted compared with PPK and dense polyetheretherketone in vitro. Moreover, in the model of rabbit femoral condyle defects, the results of micro computed tomography and histological and mechanical evaluation revealed that the ingrowth of new vessels and bone tissues into CSNPPK was significantly greater than that into PPK in vivo. Furthermore, the load-displacement and push-out loads for CSNPPK with bone tissues were higher than for PPK, indicating good osseointegration. In short, CSNPPK not only promoted vascularization but also enhanced osteogenesis as well as osseointegration in vivo. Therefore, it can be suggested that CSNPPK with good biocompatibility, osteogenic activity, and vascularization might be a promising candidate as an implant for bone substitute and repair.

Mesenchymal stromal cell senescence and apoptosis have been identified as critical molecular hallmarks in aging. In this study, we used stromal cell sheet culture as an in vitro model to study the progressive changes of cellular senescence, apoptosis and underlying mechanism in Wnt3a treated cells. Our results showed fresh bone marrow mesenchymal stromal cells (BMSCs) become senescent and undergo apoptosis with increased inflammatory profile and Reactive Oxygen Species (ROS) in high-density cell sheet cultures. The gene expression level of senescence related proteins and key regulators of apoptosis in cell sheet cultures was significantly increased in older BMSCs at Days 4 and 7 cultures compared with younger cells at Day 1 cultures. More importantly, Wnt signaling activation significantly reduced senescence in cell sheet cultures by direct regulation of cell cycle inhibitor p27. This study not only characterized the cellular and molecular features of aging stromal cells in short-term cell sheet cultures, but also identified the downstream target responsible for Wnt inhibition of cell senescence.

Placenta-derived mesenchymal stromal cells (PMSCs) provide a promising cell source for tissue regeneration. However, rapid induction of PMSC chondrogenic differentiation during therapeutic transplantation remains extremely challenging. Here we undertook a study to determine if Notch inhibition by soluble Jagged1 (JAG1) peptides could be utilized to accelerate PMSC-induced cartilage regeneration in a mouse post-traumatic osteoarthritis (PTOA) model. Our results showed that treatment of PMSCs with soluble JAG1 significantly enhanced chondrogenesis in culture as shown by increased alcian blue staining and decreased Notch target Hes1 expression when compared to those in lgG-treated control cells. Importantly, significantly enhanced cartilage formation and decreased joint inflammation were observed when JAG1-treated PMSCs were injected into mouse PTOA knee joints. Finally, in vivo cell tracing showed that more JAG1-treated PMSCs remained in knee joint tissues and that JAG1-treated PMSCs exhibited greater PMSC chondrogenic differentiation than lgG-treated control PMSCs at 4 weeks after injection. These data indicate that transient Notch inhibition by soluble JAG1 could be used to enhance PMSC survival and chondrogenic differentiation, thereby increasing the therapeutic potential of PMSCs for cartilage regeneration., Joint repair: Growing new cartilage from placental stem cells Stem cells derived from placental tissue may help in treating damaged joints, thanks to an improved method for encouraging them to form cartilage. Placenta-derived stem cells are readily available, as the placenta is usually discarded after birth. These stem cells can easily be grown into cartilage tissue in a laboratory, but not when transplanted. Researchers led by Yufeng Dong (Louisiana State University Health Sciences Center, Shreveport, USA) and Xifu Shang (Anhui Provincial Hospital, Hefei, China) treated stem cells with a naturally occurring protein, JAG1, which blocks the signal that prevents them from forming cartilage. They found that JAG1 increased the stem cells’ capacity for cartilage formation. When JAG1-stimulated stem cells were injected into a mouse model of joint disease, cartilage formation was improved, and joint inflammation was reduced.

Background The direct anterior approach (DAA) for total hip arthroplasty (THA) is typically performed in the supine position using a specially designed operating room table, which makes this approach more accessible to orthopedic surgeons. We attempted to perform this procedure in the lateral decubitus position on an ordinary operation table to avoid dependence on a special operating room table. There is an obvious absence of literature regarding this subject. Methods A total of 248 patients (295 hips) were recruited for primary THAs from July 1, 2014 to December 31, 2014. In total, 126 hips (42.7%) underwent THAs using the DAA in the lateral decubitus position. The technical feasibility and early results were evaluated. Results The orientation of the acetabular component was 16.5° ± 4.9° anteversion and 43.3° ± 3.5° abduction. Intraoperative proximal femoral fracture occurred in one hip. The superficial wound complications occurred in 2 hips and the hematoma in one hip while in hospital. The lateral femoral cutaneous nerve injury was noted in 43 hips. The early dislocation occurred in 2 hips. Heterotopic ossification was Brooker class I in 5 hips and class II in 1 hip. No aseptic loosening, postoperative periprosthetic fracture, and deep infection occurred in our series. Conclusion The DAA for THA in the lateral decubitus position may be a valuable alternative if the DAA in the supine position is difficult to implement owing to absence of a special operating room table. This technique also seems to provide satisfactory clinical and radiographic outcomes with an acceptable complication in our early follow-up.

Skeletal tissue development and regeneration in mammals are intricate, multistep, and highly regulated processes. Various signaling pathways have been implicated in the regulation of these processes, including Notch. Notch signaling is a highly conserved, intercellular signaling pathway that regulates cell proliferation and differentiation, determines cell fate decision, and participates in cellular process in embryonic and adult tissue. Here, we review recent data showing the regulation of Notch signaling in osteogenesis, osteoclastogenesis, and angiogenesis. These processes are cell-context–dependent via direct or indirect mechanisms. Furthermore, Notch signaling may be highly beneficial for efficient coupling of osteogenesis and angiogenesis for tissue engineering and skeletal repair, which is critical to develop clinically therapeutic options.

Bone marrow mesenchymal stem cells (BM‑MSCs) are important for postnatal angiogenesis and are suitable for use in construction of blood vessels by tissue engineering. The present study aimed to investigate the influence of recombination signal binding protein for immunoglobulin kappa J region (RBP‑JK) on the differentiation of BM‑MSCs into vascular endothelial cells, and to assess the underlying mechanisms. BM‑MSCs were isolated and identified by flow cytometry. Lentiviral vectors encoding RBP‑JK shRNA (shRBPJK) were constructed to knockdown RBP‑JK expression and endothelial differentiation of BM‑MSCs was induced. The experimental groups were treated with: empty lentiviral vector (vector group), growth factors (bFGF and VEGF; induced group), shRBPJK (shRBPJK group), and growth factors + shRBPJK (induced + shRBPJK group). The expression of endothelial markers, vascular endothelial growth factor receptor 2 (Flk‑1), and von Willebrand factor (vWF) were detected by immunofluorescence. Additionally, in vitro blood vessel formation and phagocytosis were assessed using acetylated LDL, Dil complex and the underlying molecular mechanisms evaluated by western blotting. BM‑MSCs were separated and transduced with shRBPJK to reduce RBP‑JK expression. Compared with the vector group, the expression of the endothelial cell markers, Flk‑1 and vWF, in vitro tubule formation, and phagocytosis ability increased, while the expression levels of p‑AKT/AKT and p‑NF‑κB/NF‑κB were significantly decreased (P

Acetabular reconstruction in adults with Hartofilakidis type B developmental dysplasia of the hip is a major technical challenge. The purpose of this retrospective study was to evaluate hip function and radiographic outcomes regarding high hip center at midterm follow-up.From January 1, 2007 to December 31, 2009, 37 patients who had Hartofilakidis type B developmental dysplasia of the hip underwent a primary total hip arthroplasty using a high hip center technique. Functional, radiographic, and survivorship outcomes were evaluated.Of the 37 patients, 31 patients (83.8%) were available for the mean follow-up of 6.1 years (range, 1.5-7.6 years). Thirty-one cementless cups were located at an average vertical distance of 38.1 ± 3.3 mm and at a mean horizontal distance of 35.5 ± 3.4 mm. The mean ratio of the height of the hip center was 2.4% (range, 2.0%-2.9%). The Harris Hip Scores were improved from 50.3 points (range, 38-63 points) preoperatively to 92.3 points (range, 85-100 points) at the final follow-up (P.001). Four patients continued to present with Trendelenburg gait pattern at the last follow-up. With use of revision for any reason and aseptic loosening as the end point, the 5-year survival rates were 90.3% (95% CI, 79.9%-100%) and 93.3% (95% CI, 84.3%-100%), respectively.The high hip center technique in conjunction with a cementless acetabular component seems to be a valuable alternative to achieve satisfactory midterm outcomes for Hartofilakidis type B developmental dysplasia of the hip.

To determine whether cell sheets generated with long-term passaged (P10) aging human mesenchymal stromal cells (MSCs) could be used for bone tissue regeneration as tissue engineered periosteum in a femoral allograft mouse model similar to fresh passaged (P3) young MSCs. At 3 weeks after transplantation of MSC sheets, results showed more bony callus formed between allograft and host bone ends in both young P3 MSC and aged P10 MSC sheet-wrapped groups when compared to allograft alone. At 6 weeks, while both MSC sheet-wrapped allografts showed more bony callus formation when compared to allograft alone groups, the bony callus size in aged P10 MSC sheet groups was significantly less than young P3 MSC sheet groups. Biomechanical testing confirmed that P3 MSC sheet-grafted femurs had the highest biomechanical strength in the three groups. Histology sections showed that the area of the chondriod callus in the aged P10 MSC sheet groups was significantly larger than in P3 MSC sheet groups. Finally, a significant increase of chondro-osteoclast activity was observed in the P3 MSC sheet-grafted femur. Our data demonstrates that extensive long-term culture-induced MSC aging impaired their osteogenic ability and subsequent bony callus formation, and could be used to induce cartilaginous callus formation.

Testing for genetic risk associations between Factor V Leiden (FVL) and the osteonecrosis of femoral head (ONFH) is common, however, inconsistent results have been previously obtained. To summarize results on the association of FVL mutation polymorphism with ONFH in various populations and to calculate the overall genetic risk factors, we performed a search of electronic databases including PubMed, Elsevier Science Direct, Chinese National Knowledge Infrastructure and the Chinese Biomedical Database to identify published studies correlating the FVL mutation with ONFH. Statistical analysis was performed using Review Manager (RevMan) version 5.0 and Stata statistical software (version 10). We identified 57 titles and included 7 studies comprising 481 cases and 867 controls in this meta-analysis. The groups were pooled, and a significant association between FVL mutation and increased ONFH was found (OR=4.55, 95% CI, 2.75–7.52, P

Cell cycle regulation is critical for chondrocyte differentiation and hypertrophy. Recently we identified the Notch signaling pathway as an important regulator of chondrocyte proliferation and differentiation during mouse cartilage development. To investigate the underlying mechanisms, we assessed the role for Notch signaling regulation of the cell cycle during chondrocyte differentiation. Real-time RT-PCR data showed that over-expression of the Notch Intracellular Domain (NICD) significantly induced the expression of p57, a cell cycle inhibitor, in chondrocytes. Flow cytometric analyses further confirmed that over-expression of NICD in chondrocytes enhances the G0/G1 cell cycle transition and cell cycle arrest. In contrast, treatment of chondrocytes with the Notch inhibitor, DAPT, decreased both endogenous and BMP2-induced SMAD 1/5/8 phosphorylation and knockdown of SMAD 1/5/8 impaired NICD-induced chondrocyte differentiation and p57 expression. Co-immunoprecipitation using p-SMAD 1/5/8 and NICD antibodies further showed a strong interaction of these proteins during chondrocyte maturation. Finally, RT-PCR and Western blot results revealed a significant reduction in the expression of the SMAD-related phosphatase, PPM1A, following NICD over-expression. Taken together, our results demonstrate that Notch signaling induces cell cycle arrest and thereby initiates chondrocyte hypertrophy via BMP/SMAD-mediated up-regulation of p57.

To analyze the operative modalities and outcomes of total hip arthroplasty for traumatic avascular necrosis of femoral head (ANFH).A retrospective study was conducted for 40 ANFH patients undergoing total hip arthroplasty from January 2007 to October 2011. There were 31 males and 9 females with a mean age of 49 (39-65) years. Their scores of Harris hip score and visual analogue scale (VAS) at pre- and post-operation were recorded to evaluate the clinical outcomes and assess the location of prosthesis by radiology.All of them were followed for an average of 31 (19-51) months. All incisions healed with first intention. There was no prosthetic infection, hip dislocation, deep vein thrombosis or nerve injury. The scores of Harris hip and VAS at Month 1 post-operation and the last follow-up were significantly higher than those preoperative ones (P0.05). And the Harris hip score of the last follow-up was also significantly higher than that at Month 1 post-operation (P0.05). However, no significant difference existed in VAS score (P0.05). The outcomes were excellent (n = 28), good (n = 9) and fair (n = 3) with an excellent and good rate of 92.5%. Possible loosing occurred in 1/11 cemented cases while bone stability was achieved in all 29 cementless cases. And 2 case had Brooker type I heterotopic bone without treatment.Total hip arthroplasty for traumatic ANFH can achieve satisfactory clinical efficacies with careful preoperative planning and intraoperative precision.

Recently we have demonstrated the importance of RBPjk-dependent Notch signaling in the regulation of mesenchymal stem cell (MSC) differentiation during skeletogenesis both in vivo and in vitro. Here we further performed RBPJK loss-of-function experiments to demonstrate for the first time that RBPJK deficient MSC shows enhanced differentiation and osteogenesis acts via up-regulation of the BMP signaling. In the present study, we first compared the spontaneous and osteogenic differentiation in normal and recombination signal binding protein for immunoglobulin kappa J region (RBPJK) deficient human bone marrow-derived mesenchymal stem cells (MSCs). It was found that RBPJK highly expressed in fresh isolated MSCs and its expression was progressing down-regulated during spontaneous differentiation and even greater in osteogenic media inducted differentiation. Deletion of RBPJK in MSCs not only enhances cell spontaneous differentiation, but also significantly accelerates condition media inducted osteogenic differentiation by showing enhanced alkaline phosphatase (ALP) activity, Alizarin red staining, gene expression of Runx2, Osteopontin (OPN), Type I collagen (COL1a1) in culture. Additionally, BMP signaling responsive reporter activity and phosphor-smad1/5/8 expression were also significantly increased upon removal of RBPJK in MSCs. These data proved that inhibition of Notch signaling in MSCs promotes cell osteogenic differentiation by up-regulation of BMP signaling, and RBPJK deficient MSC maybe a better cell population for cell-based bone tissue engineering.