rec PDGF BB (human)

The highly invasive behavior of glioblastoma cells contributes to the morbidity and mortality associated with these tumors. The integrin-mediated adhesion and migration of glioblastoma cells on brain matrix proteins is enhanced by stimulation with growth factors, including platelet-derived growth factor (PDGF). As focal adhesion kinase (FAK), a nonreceptor cytoplasmic tyrosine kinase, has been shown to promote cell migration in various other cell types, we analysed its role in glioblastoma cell migration. Forced overexpression of FAK in serum-starved glioblastoma cells plated on recombinant (rec)-osteopontin resulted in a twofold enhancement of basal migration and a ninefold enhancement of PDGF-BB-stimulated migration. Both expression of mutant FAK(397F) and the downregulation of FAK with small interfering (si) RNA inhibited basal and PDGF-stimulated migration. FAK overexpression and PDGF stimulation was found to increase the phosphorylation of the Crk-associated substrate (CAS) family member human enhancer of filamentation 1 (HEF1), but not p130CAS or Src-interacting protein (Sin)/Efs, although the levels of expression of these proteins was similar. Moreover downregulation of HEF1 with siRNA, but not p130CAS, inhibited basal and PDGF-stimulated migration. The phosphorylated HEF1 colocalized with vinculin and was associated almost exclusively with 0.1% Triton X-100 insoluble material, consistent with its signaling at focal adhesions. FAK overexpression promoted invasion through normal brain homogenate and siHEF1 inhibited this invasion. Results presented here suggest that HEF1 acts as a necessary and specific downstream effector of FAK in the invasive behavior of glioblastoma cells and may be an effective target for treatment of these tumors.

Background: The goal of the present study was to create a new biodegradable hybrid PCL-P (HEMA-NIPAAm) thermosensitive hydrogel scaffold by grafting PNIPAAm-based copolymers with biodegradable polyesters to promote the chondrogenic differentiation of human progenitor cells (adipose-derived stem cells-hASCs) in the presence of the platelet-derived growth factor (PDGF-BB). Different mixture ratios including 50 mmol ε-caprolactone and 10 mmol HEMA (S-1), 30 mmol ε-caprolactone and 10 mmol HEMA (S-2), 10 mmol ε-caprolactone and 30 mmol HEMA (S-3) were copolymerized followed by the addition of NIPAAm. Results: A mild to moderate swelling and wettability rates were found in S-2 group copmpared to the S-1 ans S-3 samples. After 7 weeks, S-2 degradation rate reached ~ 43.78%. According to the LCST values, S-2, reaching 37 °C, was selected for different in vitro assays. SEM imaging showed nanoparticulate structure of the scaffold with particle size dimensions of about 62-85 nm. Compressive strength, Young's modulus, and compressive strain (%) of S-2 were 44.8 MPa, 0.7 MPa, and 75.5%. An evaluation of total proteins showed that the scaffold had the potential to gradually release PDGF-BB. When hASCs were cultured on PCL-P (HEMA-NIPAAm) in the presence of PDGF-BB, the cells effectively attached and flattened on the scaffold surface for a period of at least 14 days, the longest time point evaluated, with increased cell viability rates as measured by performing an MTT assay (p < 0.05). Finally, a real-time RT-PCR analysis demonstrated that the combination of PCL-P (HEMA-NIPAAm) and PDGF-BB promoted the chondrogenesis of hASCs over a period of 14 days by up-regulating the expression of aggrecan, type-II collagen, SOX9, and integrin β1 compared with the non-treated control group (p < 0.05). Conclusion: These results demonstrate that the PCL-P(HEMA-NIPAAm) hydrogel scaffold carrying PDGF-BB as a matrix for hASC cell seeding is a valuable system that may be used in the future as a three-dimensional construct for implantation in cartilage injuries.

Aim: To assess whether the use of deproteinized bovine bone mineral (DBBM) and native bilayer collagen membrane (NBCM) improved healing of peri-implantitis-related bone defects at 12 months. Materials and methods: In a multi-centre, randomized clinical trial, 32 individuals received surgical debridement (control group [CG]), and 34 received adjunct use of DBBM and NBCM (test group [TG]). Radiographic defect fill (RDF), probing pocket depth (PPD), bleeding on probing (BOP), suppuration (SUP), recession (REC), cytokines (IL-1β, IL-1RA, IL-6, IL-8, IL-12, IP10, PDGF-BB, TNF-α, VEGF), and patient-reported outcomes (PROs) were evaluated at 3, 6, 9, and 12 months. Results: RDF at the deepest site amounted 2.7 ± 1.3 mm in TG and 1.4 ± 1.2 mm in CG (p <.0001). PPD was reduced by 1.9 mm in TG and 2.3 mm in CG (p = .5783). There were no significant differences between groups regarding reductions of BOP, SUP, REC, cytokines levels, or oral health impact profile (OHIP)-14 scores at 12 months. Successful treatment (RDF ≥ 1.0 mm, PPD ≤5 mm, ≤1/4 site with BOP grade 1, no SUP) was identified in 32% in TG and 21% in CG. Conclusions: DBBM and NBCM resulted in significantly more RDF than debridement alone. No difference was found in any clinical parameters or PROs between the groups. ClinicalTrials.gov Identifier: NCT02375750.