scholarly journals High Glucose Potentiates Collagen Synthesis and Bone Morphogenetic Protein-2-Induced Early Osteoblast Gene Expression in Rat Spinal Ligament Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (1) ◽  
pp. 63-74 ◽  
Author(s):  
Hai Li ◽  
Lei-Sheng Jiang ◽  
Li-Yang Dai

Abstract Type 2 diabetes mellitus (T2DM) is an independent risk factor for ossification of the posterior longitudinal ligament, but the mechanism is unclear. We isolated cells from rat cervical spine ligaments and studied the effects of high glucose on expression of osteoblast genes to provide insight into molecular mechanism. Using these cells, high glucose stimulated the synthesis of type I collagen and significantly potentiated expression of early osteoblast genes (Runx2; alkaline phosphatase, ALP; and osteopontin, OP) induced by bone morphogenetic protein-2 (BMP-2). Notably, these effects of high glucose were fully mimicked and augmented by H2O2, although blocked by the reactive oxygen species inhibitor N-acetyl cysteine. Furthermore, exposure of these cells to high glucose significantly suppressed the phosphorylation of p38MAPK while enhancing the phosphorylation of protein kinase C (PKC) in the cells. Consistent with these observations, an inhibitor of p38 augmented the potentiation of high glucose on BMP-2-induced early osteogenic gene expression, whereas the PKC inhibitor repressed the effect of high glucose on type I collagen synthesis of the cells. In conclusion, high glucose, via production of reactive oxygen species, subsequent activation of PKC, and inhibition of p38, enhances type I collagen synthesis and expression of early osteogenesis genes induced by BMP-2 in rat spinal ligament cells. Hyperglycemia may play an important role in the onset or progression of ossification of the posterior longitudinal ligament by promoting the responsiveness of ligament cells to osteogenic differentiation.

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yangyang Li ◽  
Yongfeng Zhang ◽  
Weiqi Meng ◽  
Yutong Li ◽  
Tao Huang ◽  
...  

Yishen Bugu Ye (YSBGY), a traditional Chinese medicine comprising 12 types of medicinal herbs, is often prescribed in China to increase bone strength. In this study, the antiosteoporotic effects of YSBGY were investigated in C57BL/6 mice afflicted with dexamethasone- (Dex-) induced osteoporosis (OP). The results showed that YSBGY reduced the interstitial edema in the liver and kidney of mice with Dex-induced OP. It also increased the number of trabecular bone elements and chondrocytes in the femur, promoted cortical bone thickness and trabecular bone density, and modulated the OP-related indexes in the femur and tibia of OP mice. It also increased the serum concentrations of type I collagen, osteocalcin, osteopontin, bone morphogenetic protein-2, bone morphogenetic protein receptor type 2, C-terminal telopeptide of type I collagen, and runt-related transcription factor-2 and reduced those of tartrate-resistant acid phosphatase 5 and nuclear factor of activated T cells in these mice, suggesting that it improved osteoblast differentiation and suppressed osteoclast differentiation. The anti-inflammatory effect of YSBGY was confirmed by the increase in the serum concentrations of interleukin- (IL-) 33 and the decrease in concentrations of IL-1, IL-7, and tumor necrosis factor-α in OP mice. Furthermore, YSBGY enhanced the serum concentrations of superoxide dismutase and catalase in these mice, indicating that it also exerted antioxidative effects. This is the first study to confirm the antiosteoporotic effects of YSBGY in mice with Dex-induced OP, and it showed that these effects may be related to the YSBGY-induced modulation of the osteoblast/osteoclast balance and serum concentrations of inflammatory factors. These results provide experimental evidence supporting the use of YSBGY for supporting bone formation in the clinical setting.


2003 ◽  
Vol 82 (1) ◽  
pp. 23-27 ◽  
Author(s):  
M. Zhao ◽  
J.E. Berry ◽  
M.J. Somerman

As an approach for improving the outcome and predictability of periodontal regenerative therapies, we have focused on determining the responses of cells within the local environment to putative regenerative factors. This study examined the effects of bone morphogenetic protein-2 (BMP-2) on murine cementoblasts in vitro. Northern blot analysis indicated that BMP-2 decreased mRNA levels of bone sialoprotein and type I collagen dose-dependently (10–300 ng/mL). At low doses, up to 100 ng/mL, BMP-2 had no effect on transcripts for osteocalcin and osteopontin, whereas at 300 ng/mL, BMP-2 greatly increased expression of these two genes. BMP-2 also inhibited cementoblast-mediated mineral nodule formation in a dose-dependent manner (inhibition was noted at 10 ng/mL). Noggin reversed the effects of BMP-2 on gene expression and on mineralization. These findings reflect the diverse responses of periodontal cells to BMP-2 and highlight the need to consider the complexity of factors involved in designing predictable regenerative therapies.


2002 ◽  
Vol 30 (3) ◽  
pp. 251-259 ◽  
Author(s):  
K Kusumoto ◽  
K Bessho ◽  
K Fujimura ◽  
J Akioka ◽  
Y Okubo ◽  
...  

Heterotopic osteoinduction in a muscle of a medium-sized, non-human primate (Japanese macaque monkey; Macaca fuscata) was investigated with recombinant human bone morphogenetic protein-2 (rhBMP-2) mixed with atelopeptide type I collagen as the carrier. Nine monkeys were divided into three groups of three: groups I (1.25 mg rhBMP-2), II (250 μg rhBMP-2) and III (50 μg rhBMP-2). Four weeks after implanting into the calf muscle pouch, the implant was examined radiographically and histologically. In one specimen of three in group I, marked radio-opaque shadow, massive chondrogenesis and partial osteogenesis were observed. In the other two specimens, only microscopic calcification signs were recognized. In groups II and III, no findings of heterotopic osteoinduction were radiographically observed; however, nuclei from muscle bundles reacted to rhBMP-2 and were large and round, as in muscle bundles near the site of osteogenesis in group I. A positive control study using rats was carried out in parallel. This was a dose-finding study, with the monkeys in group III acting as a sub-effective dose (placebo) control, and rats acting as an active control, or verum, to show that the techniques are sufficiently sensitive. Bone morphogenetic protein appears to osteoinduce less bony material in soft tissue in primates than in rats.


1997 ◽  
Vol 86 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Gregory A. Helm ◽  
Jonas M. Sheehan ◽  
Jason P. Sheehan ◽  
John A. Jane ◽  
Charles G. diPierro ◽  
...  

✓ Autologous bone grafts are currently considered “gold standard” material for achieving long-term spinal arthrodesis. The present study was performed to determine whether demineralized bone matrix (DBM), type I collagen gels, or bone morphogenetic protein-2 (BMP-2) can improve autologous bone spinal fusions. Using a unilateral decompression—contralateral fusion technique in dogs, each of these materials was added to an autologous bone graft. Volumetric analysis, histological analysis, and biomechanical testing were performed to assess the effectiveness of each material. The DBM had an inhibitory effect on solid bone fusion of the spine, whereas the type I collagen gels improved the bony interface between the graft and the host spine. The BMP-2 strongly enhanced the amount of bone deposition at the fusion site and increased the number of intervertebral levels that were solidly fused. This study strongly supports the use of BMP-2 as an additive to autologous bone grafts in spine stabilization.


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