scholarly journals Association of Bone Morphogenetic Protein (BMP)/Smad Signaling Pathway with Fracture Healing and Osteogenic Ability in Senile Osteoporotic Fracture in Humans and Rats

2018 ◽  
Vol 24 ◽  
pp. 4363-4371 ◽  
Author(s):  
De-Bao Liu ◽  
Cong Sui ◽  
Ting-Ting Wu ◽  
Lian-Zhong Wu ◽  
You-Yu Zhu ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Osteoporotic Fracture ◽  
Smad Signaling ◽  
Morphogenetic Protein ◽  
Smad Signaling Pathway

The protective effects of bone morphogenetic protein-7 against epithelial injury and matrix metalloproteases upregulation induced by silica in vitro

2016 ◽  
Vol 36 (9) ◽  
pp. 892-900 ◽  
Author(s):  
D Liang ◽  
G An ◽  
Z Zhu ◽  
Y Wang ◽  
G Yang ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Neutralizing Antibody ◽  
Collagen I ◽  
Bone Morphogenetic Protein 7 ◽  
Smad Signaling ◽  
Morphogenetic Protein ◽  
Smad Signaling Pathway

Objective: We investigate the effects of bone morphogenetic protein-7 (BMP-7) on models with silica-induced and macrophage-mediated fibrosis and its possible mechanisms in vitro. Methods: Rat alveolar II epithelial (RLE-6TN) cells were incubated with the supernatant of mouse macrophage-like cells (RAW264.7) and treated with 0, 25, 50, and 100 μg/mL silica. Using Western blotting, the epithelial markers (surfactant proteins-C and E-cadherin) and the mesenchymal markers (fibronectin (FN) and viminten (Vim)) were detected. After neutralizing the BMP-7, the progress of fibrosis was assessed by the content of hydroxyproline (Hyp) and collagen I, III protein levels as well as the Smad signaling pathway proteins, including phosphorylated Smad1/5(P-Smad1/5) and phosphorylated Smad2/3(P-Smad2/3). Collagen I was also identified by immunofluorescence and pretreated with SB-431542, LDN-193189, or anti-BMP-7-neutralizing antibody. In addition, the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 were detected using Western blotting. Results: The model of RLE-6TN cells was established successfully, the expressions of Vim, FN, MMP-2, and MMP-9 were upregulated, while the concentration of silica is increased. Neutralizing BMP-7 stimulated the decrease of P-Smad1/5 and the increase of P-Smad2/3, as well as the collagen I, collagen III, FN, and Hyp via Smad signaling pathway. Furthermore, pretreated with LDN-193189 or anti-BMP-7-neutralizing antibody, the expression of collagen I was increased, yet it was decreased with SB-431542 intervention. Conclusion: The activated BMP/Smad and suppressed transforming growth factor-β/Smad pathways could suppress silica-induced fibrosis via a MMP-dependent mechanism. BMP-7 is expected to be the optimized strategy of delaying the interstitial changes.

scholarly journals Serum and liver iron differently regulate the bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway in mice

Hepatology ◽  
2011 ◽  
Vol 54 (1) ◽  
pp. 273-284 ◽  
Author(s):  
Elena Corradini ◽  
Delphine Meynard ◽  
Qifang Wu ◽  
Shan Chen ◽  
Paolo Ventura ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Liver Iron ◽  
Smad Signaling ◽  
Morphogenetic Protein ◽  
Smad Signaling Pathway ◽  
Bone Morphogenetic Protein 6

scholarly journals Endogenous Parathyroid Hormone Promotes Fracture Healing by Increasing Expression of BMPR2 through cAMP/PKA/CREB Pathway in Mice

2017 ◽  
Vol 42 (2) ◽  
pp. 551-563 ◽  
Author(s):  
Wei Zhou ◽  
Lipeng Yu ◽  
Jin Fan ◽  
Bowen Wan ◽  
Tao Jiang ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Fracture Healing ◽  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Male Mice ◽  
Morphogenetic Protein ◽  
Significant Difference ◽  
Creb Pathway

Background/Aims: Endogenous parathyroid hormone (PTH) plays an important role in fracture healing. This study investigated whether endogenous PTH regulates fracture healing by bone morphogenetic protein (BMP) and/or the transforming growth factor-β (TGF-β) signaling pathway. Methods: Eight-week-old wild-type (WT) and PTH-knockout (PTH KO) male mice were selected, and models of open right-femoral fracture were constructed. Fracture healing and callus characteristics of mice in the two groups were compared by X-ray, micro-computed tomography, histological, and immunohistochemical examinations. Bone marrow mesenchymal stem cells (BMMSCs) of 8-week-old WT and PTHKO male mice were obtained and induced into osteoblasts and chondrocytes. Results: We found that expression levels of Runt-related transcription factor (RUNX2), bone morphogenetic protein-receptor-type Ⅱ (BMPR2), phosphorylated Smad 1/5/8, and phosphorylated cyclic adenosine monophosphate-responsive element binding protein (CREB) in the callus of PTHKO mice were significantly decreased, whereas no significant difference in expression of SOX9, TGF-βR2,or pSMAD2/3 was observed between PTHKO and WT mice. Additionally, the activity of osteoblast alkaline phosphatase was low at 7 days post-induction, and was upregulated by addition of PTH or dibutyryl cyclic adenosine monophosphate (dbcAMP) to the cell culture. Furthermore, H89 (protein kinase A inhibitor)eliminated the simulating effects of PTH and dbcAMP, and a low concentration of cyclic adenosine monophosphate (cAMP) was observed in PTHKO mouse BMMSCs. Conclusion: These results suggested that endogenous PTH enhanced BMPR2 expression by a cAMP/PKA/CREB pathway in osteoblasts, and increased RUNX2 expression through transduction of the BMP/pSMAD1/5/8 signaling pathway.

Icariin Accelerates Fracture Healing via Activation of the WNT1/β-catenin Osteogenic Signaling Pathway

2020 ◽  
Vol 21 (15) ◽  
pp. 1645-1653
Author(s):  
Xiao-Yun Zhang ◽  
Yue-Ping Chen ◽  
Chi Zhang ◽  
Xuan Zhang ◽  
Tian Xia ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Fracture Healing ◽  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Type I Collagen ◽  
Type I ◽  
Alp Activity ◽  
Morphogenetic Protein ◽  
Osteogenic Signaling

Background: Icariin has been shown to enhance bone formation. Objective: The present study aimed to investigate whether icariin also promotes bone fracture healing and its mechanisms. Methods: First, we isolated and cultured rat bone marrow stromal cells (rBMSCs) with icariincontaining serum at various concentrations (0%, 2.5%, 5% and 10%) and then measured alkaline phosphatase (ALP) activity and the expression of Core-binding factor, alpha 1 (Cbfα1), bone morphogenetic protein-2 (BMP-2) and bone morphogenetic protein-4 (BMP-4) in the rBMSCs. Second, we established a model of fracture healing in rats and performed gavage treatment for 20 days. Then, we detected bone biochemical markers (ELISA kits) in the serum, fracture healing (digital radiography, DR), and osteocalcin expression (immunohistochemistry). Results: Icariin treatment increased ALP activity and induced the expression of Cbfα1, BMP-2 and BMP-4 in rBMSCs in a dose-dependent manner. In addition, Icariin increased the serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), N-terminal telopeptides of type I collagen (NTX-1), C-terminal telopeptide of type I collagen (CTX-1) and tartrate-resistant acid phosphatase 5b (TRACP-5b); promoted osteocalcin secretion at the fracture site; and accelerated fracture healing. Conclusions: Icariin can promote the levels of bone-formation markers, accelerate fracture healing, and activate the WNT1/β-catenin osteogenic signaling pathway.

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