Insulin receptor substrate 1 regulates the cellular differentiation and the matrix metallopeptidase expression of preosteoblastic cells

Bu, Yanhong; He, Yuan; Zhou, Hong-Hao; Liu, Wei; Peng, Dan; Tang, Anliu; Tang, Lingli; Xie, Hong; Huang, Qiuxia; Luo, Xiang‐Hang; Liao, Er-Yuan

doi:10.1677/joe-10-0064

Cited by 25 publications

(18 citation statements)

References 28 publications

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“…(39) IRS-1 knockout mice had blunted stimulation of bone turnover after 4 weeks of PTH compared to controls. Knockdown of IRS-1 using RNA interference in cultured osteoblasts leads to impaired collagen-1 synthesis and differentiation.…”

Section: Discussionmentioning

confidence: 97%

IRS-1 Functions as a Molecular Scaffold to Coordinate IGF-I/IGFBP-2 Signaling During Osteoblast Differentiation

Shen

Rosen

et al. 2016

Journal of Bone and Mineral Research

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Insulin like growth factor I (IGF-I) and insulin like growth factor binding protein-2 (IGFBP-2) function coordinately to stimulate AKT and osteoblast differentiation. IGFBP-2 binding to receptor protein tyrosine phosphatase β (RPTPβ) stimulates polymerization and inactivation of phosphatase activity. Because phosphatase and tensin homolog (PTEN) is the primary target of RPTPβ, this leads to enhanced PTEN tyrosine phosphorylation and inactivation. However RPTPβ inactivation also requires IGF-I receptor activation. The current studies were undertaken to determine the mechanism by which IGF-I mediates changes in RPTPβ function in osteoblasts. IGFBP-2/IGF-I stimulated vimentin binding to RPTPβ and this was required for RPTPβ polymerization. Vimentin serine phosphorylation mediated its binding to RPTPβ and PKCζ was identified as the kinase that phosphorylated vimentin. To determine the mechanism underlying IGF-I stimulation of PKCζ-mediated vimentin phosphorylation, we focused on insulin receptor substrate–1 (IRS-1). IGF-I stimulated IRS-1 phosphorylation and recruitment of PKCζ and vimentin to phospho-IRS-1. IRS-1 immunoprecipitates containing PKCζ and vimentin were used to confirm that activated PKCζ directly phosphorylated vimentin. PKCζ does not contain a SH-2 domain that is required to bind to phospho-IRS-1. To determine the mechanism of PKCζ recruitment we analyzed the role of p62 (a PKCζ binding protein) that contains a SH2 domain. Exposure to differentiation medium plus IGF-I stimulated PKCζ/p62 association. Subsequent analysis showed the p62/PKCζ complex was co-recruited to IRS-1. Peptides that disrupted p62/PKCζ or p62/IRS-1 inhibited IGF-I/IGFBP-2 stimulated PKCζ activation, vimentin phosphorylation, PTEN tyrosine phosphorylation, AKT activation, and osteoblast differentiation. The importance of these signaling events for differentiation was confirmed in primary mouse calvarial osteoblasts. These results demonstrate the cooperative interaction between RPTPβ and the IGF-I receptor leading to a coordinated series of signaling events that are required for osteoblast differentiation. Our findings emphasize the important role IRS-1 plays in modulating these signaling events and confirm its essential role in facilitating osteoblast differentiation.

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Section: Discussionmentioning

confidence: 97%

IRS-1 Functions as a Molecular Scaffold to Coordinate IGF-I/IGFBP-2 Signaling During Osteoblast Differentiation

Shen

Rosen

et al. 2016

Journal of Bone and Mineral Research

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“…However, the potential cellular mechanism remains unclear. Several studies have demonstrated that insulin receptor substrates (IRS-1 and IRS-2) that mediate intracellular signaling by insulin and IGF are essential for the RANKL expression in osteoclasts (27)(28)(29). To make clear the potential cellular mechanism of RANKL expression regulated by insulin, future studies can take into account these 2 substrate-mediated signaling pathways activated by insulin in osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

Insulin effect on RANKL and OPG expression in human osteoblast-like MG63 cells

Wang¹,

Zhong²

2013

Turk J Med Sci

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A simple method for simultaneous pre-concentration of Cu, Ni, and Co metal ions prior to their determination by flame atomic absorption spectrometry is reported. The method is based on the extraction of target ions via complexation with indane-1,2,3-trione 1,2-dioxime immobilized on sodium dodecyl sulfate (SDS) coated alumina. The metal content on the adsorbent was eluted with 4.5 mL of 2 mol L −1 nitric acid. The influences of the analytical parameters including pH, sample volume and flow rate, and eluent type and flow rate were investigated. The effect of matrix ions on the retentions of the analytes was also examined. The recoveries of analytes were generally higher than 96% with a low relative standard deviation (R.S.D. < 3%). The presented method was successfully applied for determination of these metals in water samples.

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“…MC3T3-E1 cells, a mouse osteoblastic cell line, were kindly provided by Professor Eryuan Liao (19). MC3T3-E1 cells were cultured in α-MEM supplemented with 10% FBS and 1% penicillin-streptomycin in 5% CO 2 at 37˚C.…”

Section: Methodsmentioning

confidence: 99%

Bezafibrate prevents palmitate-induced apoptosis in osteoblastic MC3T3-E1 cells through the NF-κB signaling pathway

Zhong

Xiu²,

Wei³

et al. 2011

Int J Mol Med

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Abstract. Osteoporosis is a bone condition defined by low bone mass and increase of fracture risk due to imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Low bone mass is likely to be due to the alteration of the osteoclast and osteoblast lifespan through regulated apoptosis. Saturated fatty acid (SFA) intake is negatively associated with bone mineral density (BMD). Furthermore, SFA induces apoptosis in osteoblastic cell lines. Bezafibrate could increase bone mass in intact male rats principally through increasing periosteal bone formation. At present, it is unknown whether bezafibrate attenuates palmitate-induced apoptosis in MC3T3-E1 cells. In the present study, we found that palmitate stimulated the degradation of IκBα and NF-κB translocation, as well as up-regulation of NF-κB-mediated Fas expression in obsteoblastic MC3T3-E1 cells. Furthermore, the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) could restore palmitate-induced caspase-3 decrease and inhibit palmitate-induced cleaved caspase-3 increase. We observed that bezafibrate, a dual ligand for the peroxisome proliferatoractivated receptors α (PPARα) and PPARδ, significantly attenuated the palmitate-induced cytotoxicity as determined by the MTT assay and inhibited the palmitate-induced apoptosis as determined by a flow cytometry assay using Annexin V-FITC/PI and assessment of the activity of caspase-3. Pre-treatment of bezafibrate prevented palmitate-induced NF-κB activation. Therefore, these findings indicate that bezafibrate inbibits palmitate-induced apoptosis via the NF-κB signaling pathway. Our results point to bezafibrate as a new strategy to attenuate bone loss associated with high fat diet beyond its lipid-lowering actions.

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Insulin receptor substrate 1 regulates the cellular differentiation and the matrix metallopeptidase expression of preosteoblastic cells

Cited by 25 publications

References 28 publications

IRS-1 Functions as a Molecular Scaffold to Coordinate IGF-I/IGFBP-2 Signaling During Osteoblast Differentiation

IRS-1 Functions as a Molecular Scaffold to Coordinate IGF-I/IGFBP-2 Signaling During Osteoblast Differentiation

Insulin effect on RANKL and OPG expression in human osteoblast-like MG63 cells

Bezafibrate prevents palmitate-induced apoptosis in osteoblastic MC3T3-E1 cells through the NF-κB signaling pathway

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