microRNA‐96 promotes osteoblast differentiation and bone formation in ankylosing spondylitis mice through activating the Wnt signaling pathway by binding to SOST

2019 ◽  
Vol 120 (9) ◽  
pp. 15429-15442 ◽  
Author(s):  
Shu Ma ◽  
Dan‐Dan Wang ◽  
Cheng‐Yuan Ma ◽  
Yan‐Dong Zhang
Keyword(s):  
Ankylosing Spondylitis ◽  
Bone Formation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Osteoblast Differentiation ◽  
Wnt Signaling Pathway

Myeloma Cells Suppress Osteoblast Differentiation by Secreting a Soluble Wnt Inhibitor, sFRP-2.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2356-2356 ◽  
Author(s):  
Takashi Oshima ◽  
Masahiro Abe ◽  
Jin Asano ◽  
Tomoko Hara ◽  
Kenichi Kitazoe ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Osteoblast Differentiation ◽  
Wnt Signaling Pathway ◽  
Bone Destruction ◽  
Nodule Formation ◽  
Mrna Levels

Abstract Multiple myeloma (MM), a malignancy of plasma cells, develops in the bone marrow, and generates devastating bone destruction. Along with enhanced bone resorption, clinical evidence has also suggested suppression of bone formation as a contributing factor to the bone loss in MM. In contrast to recent understanding on mechanisms of osteolysis enahnced in MM, little is known about factors responsible for impaired bone formation. A canonical Wingless-type (Wnt) signaling pathway has recently been shown to play a critical role in osteoblast differentiation. Therefore, in the present study, we aimed to clarify mechanisms of suppression of osteoblast differentiation by MM cells with a particular focus on a canonical Wnt signaling pathway. Because several secreted Frizzled related protein (sFRP) and DKK family members are known as soluble Wnt antagonists, we first examined the expression of sFRP-1, 2 and 3 and DKK-1 in MM cell lines including U266, RPMI8226 and ARH77. All cell lines expressed sFRP-2 and sFRP-3 mRNA observed by RT-PCR. However, sFRP-1 was not expressed in any cell line, and Dkk-1 was expressed only in U266 cells at mRNA levels. We next conducted Western blot analyses for these factors and detected only sFRP-2 in immunoprecipitants of conditioned media as well as cell lysates of all these cell lines. However, no other factors were found at protein levels. Furthermore, sFRP-2 mRNA and protein expression was detected in most MM cells from patients with advanced or terminal stages of MM with bone destruction including plasma cell leukemia (3/4 and 8/10, respectively). In order to examine a biological role for sFRP-2, we added recombinant sFRP-2 to MC3T3-E1 cell culture together with BMP-2. Exogenous sFRP-2 partially suppressed alkaline phosphatase activity but almost completely mineralized nodule formation enhanced by BMP-2. Furthermore, sFRP-2 immunodepletion significantly restored mineralized nodule formation in MC3T3-E1 cells suppressed by RPMI8226 and ARH77 CM. These results suggest that sFRP-2 alone is able to suppress osteoblast differentiation induced by BMP-2 and that MM cell-derived sFRP-2 is among predominant factors responsible for defective bone formation in MM. Because MM cell-derived factors such as DKK-1, IGF-BP4 and IL-3 other than sFRP-2 have been implicated as an inhibitor of osteoblast differentiation, sFRP-2 may act alone or in combination with such other factors to potently suppress bone formation in MM. Taken together, MM cells may cause an imbalance of bone turnover with enhanced osteoclastic bone resorption and concomitantly suppressed bone formation, which leads to devastating destruction and a rapid loss of bone.

Frizzled 6 disruption suppresses osteoblast differentiation induced by nanotopography through the canonical Wnt signaling pathway

2020 ◽  
Vol 235 (11) ◽  
pp. 8293-8303
Author(s):  
Rodrigo Paolo Flores Abuna ◽  
Fabiola Singaretti Oliveira ◽  
Leticia Faustino Adolpho ◽  
Roger Rodrigo Fernandes ◽  
Adalberto Luiz Rosa ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Osteoblast Differentiation ◽  
Wnt Signaling Pathway ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

scholarly journals Targeting the Wnt signaling pathway to augment bone formation

2008 ◽  
Vol 6 (4) ◽  
pp. 142-148 ◽  
Author(s):  
Mohammad Shahnazari ◽  
Wei Yao ◽  
Maripat Corr ◽  
Nancy E. Lane
Keyword(s):  
Bone Formation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway

The Molecular Mechanisms of Estrogen Receptor α on Two Single Nucleotide Polymorphisms to Regulate WNT Signaling in Osteoblasts

2021 ◽  
Author(s):  
◽  
Sarocha Suthon ◽  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Bone Mass ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Osteoblast Differentiation ◽  
Association Studies ◽  
Wnt Signaling Pathway ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Osteoporosis is the most common bone metabolic disorder, affecting over 200 million people globally. It is characterized by bone mass depletion and microarchitectural deterioration, leading to bone fragility and susceptibility to bone fracture. Genetic factors, estrogen deficiency, and dysregulation of the WNT signaling pathway contribute to the development of this disease. Genome-wide association studies have predicted that the single nucleotide polymorphisms (SNPs) rs2887571 and rs9921222 associate with low bone mass, but the mechanism of these SNPs has remained unknown. Analysis of osteoblasts from 112 different joint replacement patients reveals that the genotype of rs2887571 correlates with WNT5B expression, and the genotype of rs9921222 correlates with AXIN1 expression. Mechanistically, SNP rs2887571 has less binding of ERα and NFATc1 to allele A than allele G, resulting in more expression of WNT5B in homozygous AA than homozygous GG. Furthermore, WNT5B exhibits distinct effects from other WNTs on osteoblastogenesis. WNT5B increases mesenchymal stem cell proliferation, promotes adipogenesis, and suppresses osteoblast differentiation via ROR1/2, then activates DVL2/3, Rac1/Cdc42, JNK, and SIN3A signaling, as well as inhibits ROCK2 and β-catenin activity. For SNP rs9921222, homozygous TT has a higher expression of AXIN1 than homozygous CC. Molecular analysis shows that GATA4 favors binding at rs9921222 allele T to promote AXIN1 expression; in contrast, ERα prefers to bind at allele C to suppress the expression, resulting in more expression of AXIN1 in homozygous TT than homozygous CC. Functionally, the level of AXIN1 negatively correlates with the level of active β-catenin, which enhances osteoblast differentiation. Taken together, the biological mechanisms of SNPs rs2887571 and rs9921222, which are associated with osteoporosis via the WNT signaling pathway, are revealed, as well as the inhibitory effect of WNT5B on osteoblastogenesis. These data will be the fundamental knowledge for the development of osteoporosis prediction and therapeutic strategies.

scholarly journals Effect of Pulsed Electromagnetic Field on Bone Formation and Lipid Metabolism of Glucocorticoid-Induced Osteoporosis Rats through Canonical Wnt Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Yuan Jiang ◽  
Hui Gou ◽  
Sanrong Wang ◽  
Jiang Zhu ◽  
Si Tian ◽  
...  
Keyword(s):  
Electromagnetic Field ◽  
Lipid Metabolism ◽  
Bone Formation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Pulsed Electromagnetic Field ◽  
Canonical Wnt Signaling ◽  
Pulsed Electromagnetic ◽  
Canonical Wnt

Pulsed electromagnetic field (PEMF) has been suggested as a promising method alternative to drug-based therapies for treating osteoporosis (OP), but the role of PEMF in GIOP animal models still remains unknown. This study was performed to investigate the effect of PEMF on bone formation and lipid metabolism and further explored the several important components and targets of canonical Wnt signaling pathway in GIOP rats. After 12 weeks of intervention, bone mineral density (BMD) level of the whole body increased significantly, serum lipid levels decreased significantly, and trabeculae were thicker in GIOP rats of PEMF group. PEMF stimulation upregulated the mRNA and protein expression of Wnt10b, LRP5,β-catenin, OPG, and Runx2 and downregulated Axin2, PPAR-γ, C/EBPα, FABP4, and Dkk-1. The results of this study suggested that PEMF stimulation can prevent bone loss and improve lipid metabolism disorders in GIOP rats. Canonical Wnt signaling pathway plays an important role in bone formation and lipid metabolism during PEMF stimulation.

scholarly journals Wnt signaling pathway as a regulator of bone formation and healing.

2021 ◽  
Vol 30 (1) ◽  
pp. 17-32
Author(s):  
Mohamed Elseweidy ◽  
Sahar El-Swefy ◽  
Nourhan Baraka ◽  
Sally Hammad
Keyword(s):  
Bone Formation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway

scholarly journals Correction to: Overexpression of CAV3 facilitates bone formation via the Wnt signaling pathway in osteoporotic rats

Endocrine ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 198-199
Author(s):  
Run-Bao Yang ◽  
Feng-Fei Lin ◽  
Jun Yang ◽  
Bin Chen ◽  
Ming-Hua Zhang ◽  
...  
Keyword(s):  
Bone Formation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway

Overexpression of CAV3 facilitates bone formation via the Wnt signaling pathway in osteoporotic rats

Endocrine ◽  
2018 ◽  
Vol 63 (3) ◽  
pp. 639-650
Author(s):  
Run-Bao Yang ◽  
Feng-Fei Lin ◽  
Jun Yang ◽  
Bin Chen ◽  
Ming-Hua Zhang ◽  
...  
Keyword(s):  
Bone Formation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway
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