Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due in part to transient growth factor bioavailability in vivo. Here, we report that gene delivery of PDGF-B stimulates repair of oral implant extraction socket defects. Alveolar ridge defects were created in rats and were treated at the time of titanium implant installation with a collagen matrix containing an adenoviral (Ad) vector encoding PDGF-B (5.5×108 or 5.5×109 pfu/ml), Ad encoding luciferase (Ad-Luc; 5.5×109 pfu/ml; control) or recombinant human PDGF-BB protein (rhPDGF-BB, 0.3 mg/ml). Bone repair and osseointegration were measured via backscattered SEM, histomorphometry, microcomputed tomography, and biomechanical assessments. Further, a panel of local and systemic safety assessments was performed. Results demonstrated bone repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared to Ad-Luc, with the high dose of Ad-PDGF-B more effective than the low dose. No significant dissemination of the vector construct or alteration of systemic parameters was noted. In summary, gene delivery of Ad-PDGF-B demonstrates regenerative and safety capabilities for bone tissue engineering and osseointegration in alveolar bone defects comparable to rhPDGF-BB protein delivery in vivo.

The mean GCF biomarker levels for IL-1beta and MMP-8 were most significantly elevated in T1DM subjects compared with healthy individuals during EG, not resulting from differences in the mean PI or microbial composition.

LMP1 is an intracellular scaffold protein that contains a PDZ domain and three LIM domains. LMP1 has multiple functions including regulating mesenchymal stem cell (MSC) osteogenesis. Gene delivery of LMP1 induces bone formation in vivo in heterotopic and orthotopic sites. However, little is known about the physiological function and gene regulatory mechanisms of LMP1 in MSCs at the molecular level. Periodontal ligament (PDL) cells are a unique progenitor cell population that can differentiate into multiple cell types, including osteoblasts, adipocytes or chondrocytes. This study sought to determine the physiological function and gene regulatory mechanisms of LMP1 in PDL cells at the molecular level. We show that LMP1 is upregulated in early stage of PDL cell osteogenic differentiation. Stable gene knockdown of LMP1 by shRNA inhibits DNA synthesis and corresponding cell proliferation in PDL cells, and further leads to decreased mineralization in vitro. Overexpression of LMP1 increases cell proliferation, and PDZ and ww-interacting domains are not enough to mediate this effect. Further, we found that in PDL cells, LMP1 is a downstream target gene of TGF-β1 that is an early signal critical in preosteoblast proliferation and differentiation. TGF-β1 stimulates PDL cell proliferation, however, this effect is compromised when LMP1 is knocked down. We further identified that the activation of TAK1-JNK/p38 kinase cascade is involved in the LMP1 gene regulation by TGF-β1. We conclude that LMP1 is a downstream gene of TGF-β1, involved in PDL cell proliferation. Our findings advance the understanding of the physiological function of LMP1, and define a regulatory mechanism of LMP1 in PDL progenitor cells and other MSCs.

No abstract

Greater neck girth and strength may be associated with a lower risk of sport-related concussion due to mitigation of head accelerations by the neck. However, neck strengthening exercise remains unstudied in youth athletes. Therefore, this pilot study assessed the feasibility and effect of targeted neck strengthening exercises in youth athletes. Seventeen participants were allocated to perform 8-wk manual resistance-based neck strengthening (n = 13) or control resistance exercise (n = 4) programs. Before and after the intervention, participants completed laboratory-based assessments of neck size, strength, and head kinematics during standardized test loading in each plane of motion. Descriptive statistics were calculated to compare pre-post changes between the two groups. All participants safely and successfully completed the intervention. Neck girth and strength increased in both groups, with greater increases in the neck strengthening group. Across all planes of motion, overall changes in head linear and angular velocity decreased in both groups, with greater decreases in ΔV in the neck strengthening group and greater decreases in Δω in controls. These results suggest the potential for resistance exercise training to reduce youth athletes' risk for sport-related concussion by increasing neck girth and strength. Additional research is needed to determine optimal neck strengthening programs.