Estrogen improves the proliferation and differentiation of hBMSCs derived from postmenopausal osteoporosis through notch signaling pathway

Fan, Jinzhu; Yang, Liu; Meng, Guolin; Lin, Yanshui; Wei, Bo‐Yuan; Fan, Jing; Hu, Huimin; Liu, Yanwu; Chen, Shi; Zhang, Jinkang; He, Qi-Zhen; Luo, Zhuojing; Liu, Jian

doi:10.1007/s11010-014-2021-7

Cited by 67 publications

(49 citation statements)

References 25 publications

(32 reference statements)

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“…Studies have highlighted a correlation between the Notch signaling pathway and Haju-Cheney syndrome, a disorder that results in osteoporosis [12]. The proliferation and differentiation of bone cells from osteoporotic patients could be increased due to an enhanced Notch signaling pathway; thus, that pathway deserves to be a potential target for osteoporosis treatment [13]. Delta-like 3 (DLL3), which at present has only been identified in mammals, is a divergent ligand and modulator located in the Notch signaling pathway, with variations in its expression linked to osteogenic induction [14,15].…”

Section: Introductionmentioning

confidence: 99%

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

Wang¹,

Luo²,

Liu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Osteoporosis is a commonly occurring condition marked by a loss of bone density. Previous evidence has highlighted the roles played by microRNAs as potential treatment tools for the disease. At present, the influence of long non-coding RNAs (lncRNAs) on the progression of osteoporosis remains largely unclear. Thus, an investigation was conducted into the target relationship between LINC00311, which has been reported to be highly expressed in osteoporosis, and delta-like 3 (DLL3), which is involved in the Notch signaling pathway, in connection with a series of bioinformatic methods. An osteoporotic rat model was established by means of ovariectomy (OVX) to evaluate the influence exerted by DLL3-binding LINC00311 on osteoclasts through the Notch signaling pathway. Methods: Osteoclasts were extracted from osteoporotic rats and transfected with the LINC00311-vector, shRNA-LINC00311, Notch activator, or a combination of the Notch activator and LINC00311-vector. Western blotting and RT-qPCR techniques were applied to determine the expression levels of LINC00311, DLL3, Notch1, Notch2, Jagged1, Hes-1 and TRAP in tissues and cells, while cell activity was detected by MTT assay. The cell cycle as well as the rate of apoptosis was detected by flow cytometry. The successfully established osteoporotic rats were designated into the OVX-siRNA, OVX-LINC00311 and OVX-control groups to observe the effects of LINC00311 on the proliferation and differentiation of osteoclasts. Results: Cells transfected with the LINC00311-vector exhibited increased expression levels of Notch2 and TRPA as well as increased cell activity, while decreased expression levels of DLL3, Notch1, Jagged1 and Hes-1, along with a decreased cell apoptosis rate, were observed. The opposite tendencies of these parameters were observed in the cells treated with shRNA-LINC00311. A key observation was made when the Notch signaling pathway was activated, in that the cell activity was decreased while the rate of apoptosis increased. In comparison with the OVX-control group, the expression levels of LINC00311, Notch2 and TRAP as well as the positive expression rate of TRAP all exhibited reductions, while those of DLL3, Jagged1 and Notch1 were elevated in the OVX-siRNA group. Compared with those in the sham group, in the OVX-control and OVX-LINC00311 groups, LINC00311 and the expression levels of Notch2 and TRAP were increased; however, decreased levels of DLL3, Jagged1 and Notch1 were noted. Conclusions: Taken together, the key findings of the present study suggest that LINC00311 induces proliferation and inhibits apoptosis of osteoclasts via the regulation of the Notch signaling pathway by inhibiting DLL3 expression, ultimately demonstrating that LINC00311 and its target gene DLL3 may serve as independent factors in cases of osteoporosis.

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Section: Introductionmentioning

confidence: 99%

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

Wang¹,

Luo²,

Liu³

et al. 2018

Cell Physiol Biochem

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“…Only a few gene targets have been rigorously validated by reporter assays and these are shown in Table 2. Overall, mir363-3p appears to targets genes directly or indirectly involved with apoptotic cell death (Li et al, 2016, Wang et al, 2016), and some of these genes display either functional sex differences or are responsive to estrogen (Tsukahara et al, 2006, Tsukahara, 2009, Utge et al, 2010, Sharma et al, 2011, Caliceti et al, 2013, Fan et al, 2014, Zhao et al, 2014, Shannonhouse et al, 2015). Both caspase-3 and -9 play a role in apoptotic cell death, with caspase-9 being an initiator caspase, and caspase-3, an executioner caspase.…”

Section: Resultsmentioning

confidence: 99%

Mir363-3p improves ischemic stroke outcomes in female but not male rats

Selvamani

Sohrabji

2017

Neurochemistry International

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With age, stroke prevalence is higher, and stroke outcome, worse, in women. Thus there is an urgent need to identify stroke neuroprotectants for this population. Using a preclinical stroke model, our studies focused on microRNAs (miRNAs), a class of translational repressors, as neuroprotectants. Analysis of circulating miRNA in the acute phase of stroke indicated potential neuroprotective capacity for miR363. Specifically, mir363 is elevated in serum of adult female rats that typically have small infarct volumes, but is deficient in age-matched males or middle-aged males and females, groups that have greater stroke-associated impairment. To directly test the effect of mir363 on stroke outcomes, first, adult females were treated with antagomirs to mir363 post stroke and next, middle-aged females were treated with mimic to mir363-3p post stroke. Antagomir treatment to adult females significantly increased infarct volume and impaired sensory motor performance. Reciprocally, mir363 mimic to middle-aged females reduced infarct volume, preserved forebrain microvessels and improved sensory motor performance. In the early acute stroke phase, mir363-3p mimic reduced the expression and functional activity of caspase-3, a critical component of the apoptotic cell cascade. In contrast, mir363-3p mimic treatment had no effect on stroke outcomes or caspase regulation in young males. Collectively, these studies show that mir363 is neuroprotective for stroke in females and implicates caspase-3 as a sex-specific miRNA-sensitive node for recovery from ischemic stroke.

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“…22 Notch signaling is increasingly recognized as a crucial participant in human skeletal development and homeostasis. Notch regulates chondrocytic and osteogenic differentiation, and dysregulation of Notch signaling may lead to a series of skeletal disorders such as osteosclerosis, 23 osteoporosis, 24 chondrodysplasia, 25 osteoarthritis, 26 osteosarcoma, 27 and congenital diseases or syndromes. 28 The present study confirmed that Notch receptor Notch2, Notch ligand JAG1, and target gene HES1 were up-regulated in OLF cells.…”

Section: Discussionmentioning

confidence: 99%

Notch signaling pathways in human thoracic ossification of the ligamentum flavum

Chen

Fan

et al. 2016

Journal Orthopaedic Research

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This study investigated the pathological process of Notch signaling in the osteogenesis of ligamentum flavum tissues and cells, and the associated regulatory mechanisms. Notch receptors, ligands, and target genes were identified by quantitative polymerase chain reaction (qPCR) in ligamentum flavum cells and immunohistochemistry in ligamentum flavum sections from ossification of the ligamentum flavum (OLF) patients and controls. The temporospatial expression patterns of JAG1/Notch2/HES1 in human ligamentum flavum cells during osteogenic differentiation were determined by qPCR. Lentiviral vectors for Notch2 overexpression and knockdown were constructed and transfected into ligamentum flavum cells before osteogenic differentiation to examine the function of Notch signaling pathways in the osteogenic differentiation of ligamentum flavum cells. Alkaline phosphatase, Runx2, Osterix, osteocalcin, and osteopontin mRNA levels, alkaline phosphatase activity, and Alizarin Red staining were used as indicators of osteogenic differentiation. JAG1/Notch2/ HES1 mRNA levels were up-regulated in ligamentum flavum cells from OLF patients, which increased during osteogenic differentiation. Immunohistochemical analysis suggested positive Notch2 expression at the ossification front. Down-regulation of Notch2 expression decelerated osteogenic differentiation of ligamentum flavum cells, and Notch2 overexpression promoted osteogenic differentiation of ligamentum flavum cells. Expression of Runx2 and Osterix increased in a manner similar to that of Notch2 during osteogenic differentiation of ligamentum flavum cells, and Notch2 knockdown and overexpression influenced their expression levels. Notch signaling plays an important role in OLF, and Notch may affect the osteogenic differentiation of ligamentum flavum cells via interactions with Runx2 and Osterix.ß

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Estrogen improves the proliferation and differentiation of hBMSCs derived from postmenopausal osteoporosis through notch signaling pathway

Cited by 67 publications

References 25 publications

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

Mir363-3p improves ischemic stroke outcomes in female but not male rats

Notch signaling pathways in human thoracic ossification of the ligamentum flavum

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