Notch increased vitronection adhesion protects myeloma cells from drug induced apoptosis.

Notch signaling activation was found in many human cancers including multiple myeloma. It was previously reported that notch contributes to drug resistant of myeloma cells upon chemotherapy treatment, inhibition of notch by inhibitors helped to overcome drug resistance. However, the mechanism of notch developed drug resistance is remained to be fully illustrated. In the current study, we reported that Notch signaling activation up-regulated expression of integrin αvß5 in myeloma cells companied with enhanced cells adhesion on vitronectin. Silencing Notch-1 receptor with siRNA or blocking cells with integrin αvß5 antibody reduced myeloma cells adhesion on vitronectin, importantly, vitronectin mediated adhesion confers protection of myeloma cells from drug induced apoptosis. Thus, we revealed a novel mechanism of myeloma cells resistance to drug induced apoptosis. This study first connected Notch signaling, VTN adhesion and drug resistance together. Therefore, blocking αvß5 receptor with antibody or knock down approach would be a novel promising strategy to treat MM.

Stro-1-positive BMSCs predict postoperative periprosthetic bone mineral density outcomes in uncemented total hip arthroplasty patients.

BACKGROUND: Bone marrow cell profiles are variable after total hip arthroplasty (THA), including variable levels of Stro-1+ and bone morphogenetic protein receptor (BMPRs)+ cells. We investigated the impact of bone marrow cell profiles on changes in periprosthetic bone mineral density (BMD) in uncemented THA patients. MATERIAL AND METHODS: Bone marrow aspirates were collected from the metaphyseal region of discarded femoral heads from 24 consecutive THA patients (12 men and 12 women; mean age 66.7 ± 11.0 years; range 52-87 years) treated from March 2009 to March 2011 at a single facility. Perioperative proportions of Stro-1+ and BMPR+ cells in femoral heads were assessed by flow cytometry. Follow-up examined the proximal femur Gruen zones R1 and R7 at 1 week and at 3, 6, and 12 months after THA, using dual-energy X-ray absorptiometry. Associations between BMD loss and age, gender, BMPRs+, and Stro-1+ were analyzed. RESULTS: At 3 months, R1 and R7 BMD decreased by 4.4% and 6.4%, respectively (P<0.05). At 12 months, the overall BMD decreases in R1 and R7 were 10.2% and 1%, respectively (P<0.05). Higher Stro-1+ cells proportion predicted R7 BMD increases at all time points (P<0.05) and R1 BMD increases at 6 and 12 months (P<0.05). BMPR1a+ proportion was associated with BMD increases at 6 months in the R1 region. BMPR2+ was not significantly associated with BMD (P>0.05). CONCLUSIONS: Elevated Stro-1+ bone marrow cell profile may be a useful prognostic indicator for uncemented THA patients.

3D printing polylactic acid polymer-bioactive glass loaded with bone cement for bone defect in weight-bearing area.

The treatment of bone defects in weight-bearing areas is mainly to transplant filling materials into the defect area, to provide immediate and strong support for weight-bearing. At present, the commonly used filling material is bone cement, which can only provide physical support without bone regeneration effect. The long-term stress at the interface may cause the loosening of bone cement. The ideal filling material should provide not only strong mechanical support but also promote bone regeneration. We introduce a 3D printing frame-filling structure in this study. The structure was printed with polylactic acid/bioactive glass as the frame, and bone cement as the filler. In this system, bone cement was used to provide immediate fixation, and the frame provided long-term fixation by promoting osteogenic induction and conduction between the interface. The results showed that the degradation of bioactive glass in the frame promoted osteogenic metabolism, induced M2 polarization of macrophages, and inhibited local inflammatory response. The in vivo study revealed that implantation of the frame-filling structure significantly promoted bone regeneration in the femoral bone defect area of New Zealand white rabbits. For a bone defect in a weight-bearing area, long-term stability could be obtained by bone integration through this frame-filling structure.

Effect of biodegradable magnesium-copper coatings on bone integration based on the porous structures in a rabbit model.

Biodegradable magnesium (Mg)-copper (Cu) coatings are promising in orthopedic implants to enhance osteogenesis. The present study aimed to compare the osteogenic effect of Mg-Cu coating and non-coating implants using a rabbit model. Mg/Mg-Cu coating of porous Ti6Al4V alloys was performed by the arc ion plating method. Five porous implants (smooth, porous, Mg coated, Mg-0.1Cu coated, and Mg-0.7Cu coated) were implanted into the distal femurs of the rabbits. The rabbits were sacrificed after one and two months, respectively, and the distal femurs with the implants were analyzed via micro-computed tomography (CT), double fluorescent labeling, and hard tissue biopsy to evaluate their osteogenic effect. During the two months of observation, the Mg/Mg-Cu coatings exhibited no advantages when compared with the bare porous structures in terms of bone integration; however, the porous structures were more conducive for bone ingrowth than the smooth implants. The osteogenic application of Mg-Cu coated orthopedic implants is worth further investigation. Furthermore, due to its long-term antibacterial ability, the biodegradable Mg-Cu coatings are promising in orthopedic applications.