Titanium particle-induced osteogenic inhibition and bone destruction are mediated by the GSK-3β/β-catenin signal pathway

Gu, Ye; Wang, Zhirong; Shi, Jiawei; Wang, Liangliang; Hou, Zhenyang; Guo, Xiaobin; Tao, Yunxia; Wu, Xiexing; Zhou, Wei; Liu, Yu; Wen, Zhang; Xu, Yaozeng; Yang, Huilin; Xue, Feng

doi:10.1038/cddis.2017.275

Cited by 32 publications

(31 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was highly expressed in the AS group and was also decreased after metformin administration, indicated that metformin may suppress the osteogenesis of fibroblasts in AS. Our results indicated that metformin also decreased the ALP positive staining, activity, and mRNA expression (one of the early osteogenic markers) in fibroblasts, which confirmed the phenomenon above. Besides, Bglap, also known as osteocalcin (Ocn), is a key factor to calcium deposition, was significantly decreased by metformin intervention, especially for AS fibroblasts.…”

Section: Discussionsupporting

confidence: 88%

Effect of metformin on ossification and inflammation of fibroblasts in ankylosing spondylitis: An in vitro study

Xiong

Jiang

Liu

et al. 2017

J of Cellular Biochemistry

View full text Add to dashboard Cite

Ankylosing spondylitis (AS) is an autoimmune disease characterized by fibroblasts ossification. However, effective drug therapy for AS is lacking. As an antidiabetic drug, metformin has demonstrated an antiosteogenic effect on osteoblasts in vitro. And it is also a kind of specific agonists for adenosine 5′-monophosphate activated protein kinase (AMPK), which is blocked in the process of AS. Given the role in antiosteogenesis and AMPK activating, metformin was investigated of its effect on fibroblasts harvested from capsular ligament of patients with femoral neck fracture and AS. Osteogenic specific makers (Alp, Bglap, Runx2, Bmp2, and Col1) in fibroblasts administered with metformin (20 μg/mL) were detected by ALP staining, alizarin red staining, qPCR, and Western blotting after 7 and 14 days of culture. Inflammation genes (il1-β and il6) and pathway (Pi3k, Akt, and Ampk) associated markers were also evaluated. Our results showed that osteogenic specific markers were greatly downregulated and ossification was effectively inhibited in AS fibroblasts after addition of metformin. Levels of inflammation markers were also decreased by metformin. Thus, metformin exerts potent effect on suppression of ossification and inflammation in AS fibroblasts via the activation of Pi3k/Akt and AMPK pathways, which may be developed as a potential agent for treatment of AS. K E Y W O R D Sankylosing spondylitis, fibroblasts, metformin, ossification Xiong Qin, Tongmeng Jiang, and Sijia Liu contributed equally to this work.

show abstract

Section: Discussionsupporting

confidence: 88%

Effect of metformin on ossification and inflammation of fibroblasts in ankylosing spondylitis: An in vitro study

Xiong

Jiang

Liu

et al. 2017

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…Research showed this pathway played a role in the development of osteolytic disease [30]. The importance of regulation of the Wnt/β-catenin signaling pathway has also been noted in the eld of aseptic loosening research [31,33]. β-catenin is an important part of Wnt/β-catenin signaling, which modulates transcription of Wnt target genes, including OPG [34].…”

Section: Discussionmentioning

confidence: 99%

Naringin Increases Osteoprotegerin Expression in Fibroblasts From Periprosthetic Membrane by the Wnt/β-catenin Signaling Pathway

Yang

Liu

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The osteoclast bone resorption is critical in aseptic loosening after joint replacemrent. The balance between activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) is considered to play a central role in osteoclast maturation. Fibroblasts from the periprosthetic membrane express RANKL and promote osteoclast formation. Studies have demonstrated that naringin inhibited osteoclastogenesis and wear particles-induced osteolysis. In this study, the naringin-induced OPG/RANKL effects and its underlying mechanism were studied in fibroblasts from periprosthetic membrane. Methods: Fibroblasts were isolated from the periprosthetic membrane during hip arthroplasty for revision due to aseptic loosening. Fibroblasts were cultured and treated with or without naringin and DKK-1 (the classical inhibitor of Wnt/β-catenin signaling pathway). OPG and RANKL mRNA and protein levels, gene expression of β-catenin and cyclin D1, which participate in the Wnt signaling pathway, were examined by real-time polymerase chain reaction and enzyme- linked immunosorbent assay. Results: The mRNA and protein levels of OPG were enhanced by naringin in a dose dependent manner compared to that of the non-treated control. In contrast, naringin did not affect the expression of RANKL. Importantly, DKK-1 attenuated OPG expression in fibroblasts under naringin treatment. Moreover, naringin stimulated the gene expression of β-catenin and cyclin D1 in fibroblasts and the effect could be inhibited by DKK-1.Conclusion: The results indicated that naringin enhanced OPG expression through Wnt/β-catenin signaling pathway in fibroblasts from periprosthetic membrane, which may be useful to inhibit periprosthetic osteolysis during aseptic loosening after total joint arthroplasty.

show abstract

“…GSK has been shown to modulate many transcription factors, such as AP-1, CREB, and b-catenin (29)(30)(31)(32)(33)(34). AP-1 acts as a transcription factor that regulates cell proliferation, survival, and apoptosis (35).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of GSK‐3β induces AP‐1‐mediated osteopontin expression to promote cholestatic liver fibrosis

Zhuang

Hua

et al. 2018

FASEB j.

View full text Add to dashboard Cite

The contribution of glycogen synthase kinase-3β (GSK-3β) to cholestatic liver disease (CLD) remains unknown. We investigated the role and mechanism of GSK-3β in vivo in liver tissues of patients with CLD and the bile duct ligation (BDL) mouse model and in vitro using a hepatic progenitor cell (HPC) and hepatic stellate cell (HSC) coculture system. In liver tissues of patients with CLD, expression of the inactive form of GSK-3β, phospho-GSK-3β(Ser9), was increased in HPCs. GSK-3β inhibition by SB216763 treatment aggravated liver fibrosis and elevated the expression of osteopontin (OPN) in the BDL mouse model. OPN was significantly overexpressed in liver tissues and serum from patients with CLD. In an HPC and HSC coculture system, inhibition of GSK-3β induced OPN production, which activated HSCs in a cholestatic environment. The expression of activator protein 1 (AP-1), an important downstream transcription factor of GSK-3β, was significantly increased in liver tissues of patients with CLD and SB216763-treated BDL mice. Finally, OPN expression was directly modulated by AP-1. These observations indicate that GSK-3β inhibition up-regulates OPN expression via AP-1 activation, which accelerates the progression of cholestatic liver fibrosis in patients with CLD and in BDL mice.-Zhuang, S., Hua, X., He, K., Zhou, T., Zhang, J., Wu, H., Ma, X., Xia, Q., Zhang, J. Inhibition of GSK-3β induces AP-1-mediated osteopontin expression to promote cholestatic liver fibrosis.

show abstract

Titanium particle-induced osteogenic inhibition and bone destruction are mediated by the GSK-3β/β-catenin signal pathway

Cited by 32 publications

References 36 publications

Effect of metformin on ossification and inflammation of fibroblasts in ankylosing spondylitis: An in vitro study

Effect of metformin on ossification and inflammation of fibroblasts in ankylosing spondylitis: An in vitro study

Naringin Increases Osteoprotegerin Expression in Fibroblasts From Periprosthetic Membrane by the Wnt/β-catenin Signaling Pathway

Inhibition of GSK‐3β induces AP‐1‐mediated osteopontin expression to promote cholestatic liver fibrosis

Contact Info

Product

Resources

About