The above results showed that the gopei mir 214 inhibitor or sfhapgpm scaffolds clearly promoted osteogenesis. Bone metastases are a common and devastating feature of latestage breast cancer. Therefore, for upregulated mirnas in bone fracture healing, downregulated target genes were selected, while for downregulated mirnas, upregulated target genes were selected. In this study, we aimed to investigate whether exercise could induce changes in mirna expression in bone and to study the effects of mir 214 on mechanical loadinginduced osteogenesis in. Conversely, mir 214 promotes osteoclastogenesis, and inhibits osteoblast differentiation and bone formation 10. In addition to promoting osteoclastogenesis, mir 214 can inhibit osteoblast differentiation by targeting atf4. Pc3derived exosomes inhibit osteoclast differentiation. Chinese journal of biochemistry and molecular biol, 2017, 332. Previous studies showed that mir 2143p facilitates adipocyte differentiation of bone marrowderived mesenchymal stem cells bmscs in vitro.
Atf4, encoding for a transcription factor required for osteoblast function, was. Patients who sustain a traumatic brain injury tbi are known to have a significantly quicker fracture healing time than patients with isolated fractures, but the underlying mechanism has yet to be identified. An investigation into the regulation of gene expression in. Sun q, ling s, li y, zhu m, zhang p, peng s, xie x, tang t, hong a, bian z, bai y, lu a, he f, zhang g. Transfection of antagomir208a3p and antagomirnc sangon biotech shanghai at a concentration of 200. Aavantimir214 prevents collapse of the femoral head in.
For the target of mir214, atf4 protein expression level was decreased after. However, the impact of cancerderived exosomes on bone cells remains unclear. Hyclone, resuspended in antibiotic free growth medium, and seeded in 24well plates at cell densities of 2. Supplementary figure 3 mir 214 directly targets atf4. Humanin hn, a mitochondrial derived peptide, plays cytoprotective role under various stress. R214 targets atf4 to functionally inhibit osteoblast activity in vitro.
We used luciferase assays in hek293t cells transfected with mir 214 mimic and a scrambled control to show mir 214 downregulates phlda2 protein by targeting its 3untranslated region utr. Bone formation and homeostasis are complex processes involving the differentiation and. Role of mirnas in bone and their potential as therapeutic. In our study, we showed that suppression of mir 214 gluconeogenesis is associated with. Wang x, guo b, li q, peng j, yang z, wang a, li d, hou z, lv k, kan g, cao h, wu h, song j, pan x, sun q, ling s, li y, zhu m, zhang p, peng s, xie x, tang t, hong. Supplementary figure 1 mirna screening a nd correlation analysis with reduced bone formation in human and mice. Mir 214 is an important regulator in bone homeostasis and bone related diseases including osteoporosis, osteosarcoma, and bone metastases. A negative regulator of bone formation is mir214, which targets atf4. In the bme, breast cancer cells severely alter the balanced bone formation and bone resorption driven by osteoblasts and osteoclasts.
These bone metastases can greatly decrease a patients quality of life, pose a financial burden, and even result in death. In this study, we aimed to investigate the effects of hngf6a, an analogue of hn, on osteoblast apoptosis and differentiation and the underlying mechanisms. Hngf6a inhibits oxidative stressinduced mc3t3e1 cell. Role of micrornas in progenitor cell commitment and. Pdf on oct 1, 2016, airong qian and others published mir85p targets macf1 to inhibit bone formation find, read and cite all the research you need on researchgate. In osteoblasts, our previous results demonstrate that mir 214 targets atf4 to inhibit bone formation. Microrna214 suppresses osteogenic differentiation of. Micrornas are short regulatory rnas that are able to posttranscriptionally modulate gene expression and that have crucial roles in the control of physiological and pathological processes including cancer onset, growth, and progression.
This allowed the forelimbs to have contact with the grid floor and allowed the animals to move around the cage for free access to food and water. Our previous study also identified that mir2143p could target atf4, an important osteogenic transcriptional factor, to suppress bone formation. However, in vitro overexpression of mir208a3p inhibited osteoblast differentiation. Frontiers targeting the metastatic bone microenvironment. A boneresorption surfacetargeting nanoparticle to deliver anti mir214 for osteoporosis therapy mingxiang cai,1, li yang,2, shufan zhang, jiafan liu,2 yao sun,1 xiaogang wang2 1engineering research center of tooth restoration and regeneration, department of oral implantology, school of stomatology, tongji university, shanghai, 2department of cell biology, institute of biomedicine. Evidences for a new role of mir214 in chondrogenesis scientific.
The above results showed that the gopei mir 214 inhibitor. Er stress, especially the atf4mediated pathway, has also been shown to be significantly upregulated in calcific av disease. In previous work, we showed that mir 214 directly targets activating transcription factor 4 atf4 to inhibit osteoblast activity, thus preventing bone formation. Numerous studies have examined the role of mir214 in bone formation 2628.
Studies in mice confirmed that mir 214 influenced osteoblast differentiation and bone formation in bone diseases. Particularly, mir214 was shown to inhibit bone formation by regulating atf4, and to promote osteoclastogenesis by targeting pten. In both groups, each mouse was maintained in a single cage on a 12h light12h dark cycle with free access to water and food. One study showed that mir 214 inhibited osteoblast.
Numerous studies have examined the role of mir 214 in bone formation 2628. These data provide an important foundation for further analyses of mir 214 as a key regulator of wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging. After 7 days, interscapular bat and inguinal swat were isolated and subjected to further analyses. Role of micrornas in progenitor cell commitment and osteogenic. Mc3t3e1 cells were trans fected with luciferase empty vector lucvector, atf4 3 utr reporter lucutr or. Metastatic bone disease is a consequence of disturbed bone remodeling due to pathological interactions between cancer cells and the bone microenvironment bme. In this study, we found that the upregulation of mirna26a5p induced by tbi correlated with a decrease in phosphatase and tensin homolog pten in callus formation. The balance between bone formation by osteoblasts and bone resorption by osteoclasts is important to maintain bone mass.
Postmenopausal osteoporosis is a disease in which there is a high level of bone remodeling and an imbalance between bone resorption and bone formation, resulting in decreased bone mineral density and disruption of bone microarchitecture 24. Microrna214 suppresses osteogenic differentiation of human. Therefore, therapeutic mir 214 mimics may attenuate the progression of prostate cancer bone. Endoplasmic reticulum er stress has been shown to play an important role in. In a new study yingxian li and her colleagues show that the microrna mir 214 targets atf4 in osteoblasts to negatively regulate their activity. A recent study also demonstrated that mir 214 directly targets atf4 to restrain bone formation in osteoclasts by suppressing osteoclast activity. A negative regulator of bone formation is mir 214, which targets atf4, a transcription factor modulating the gene expression of osteocalcin. Since elevated cyclic stretch is one of the major mechanical stimuli for av calcification and atf4 is a validated target of mir 214, we investigated the. Overexpression of mir214 was shown to reduce bone formation in mice. Pdf mir214 targets atf4 to inhibit bone formation researchgate. The roles of mir214 in inhibition of bone formation. Osteoclastderived exosomal mir2143p inhibits osteoblastic bone. Mir 214 was reported to regulate the process of osteogenesis and is considered a biomarker of osteoporosis. Read on microrna214 suppressing osteogenic differentiation of c2c12 myoblast cells by targeting osterix, bone on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Prostate cancer is a serious disease that can invade bone tissues. The mir199 and mir 214 genes cluster not only participates in skeleton formation, but maintains the skeleton in a healthy state as well. Taken together, we hypothesized that mir 214 might be a part of the cellular defense system in protecting erthyroid cells against oxidative stressinduced toxicity. Osteoclastic mir214 targets traf3 to contribute to. Hemeregulated eif2alpha kinase activated atf4 signaling pathway in oxidative stress and erythropoiesis.
Cell proliferation of murine osteoblastic cell line mc3tce1 was examined by cck8 assay and edu staining. On microrna214 suppressing osteogenic differentiation of. The roles of mir 214 in inhibition of bone formationj. The expression of mir34a was analyzed during the osteoblastic differentiation of irradiated bmscs and bone formation in irradiated bone defects. Similarly, mir 214 targets atf4 in osteoblasts to inhibit bone formation. Functionalization of sfhap scaffold with gopeimirna. In our study, we showed that suppression of mir 214 gluconeogenesis is associated with lower levels of atf4 protein. One study demonstrated that mir214 targeted osterix to inhibit osteogenic. Previous studies reported that mir 214 targets atf4 to inhibit bone formation and that atf4 plays a vital role in glucose metabolism 30, 55, 56. Circulating mir338 cluster activities on osteoblast. In this study, the 3t3l1 cell line was used to analyze the function of mir 2143p in vitro.
Microrna214 controls skin and hair follicle development. Microrna214 suppresses gluconeogenesis by targeting. In this study we wanted to study the molecular mechanism of mir 214 hypothesized that mir 214 induced radioresistance of osteosarcoma by targeting phlda2. Mir214 attenuates the osteogenic effects of mechanical. Based on our findings, we further investigated the mechanisms underlying mir 214 regulation of gluconeogenesis. A previous study identified that inhibition of osteogenic differentiation of bmscs leads to impaired bone formation and contributes to osteoporosis. In adult organisms, bone formation is mediated by the recruitment of bone marrow mesenchymal stem cells bmscs, which can differentiate into osteoblast cells 2,3. Pdf mir85p targets macf1 to inhibit bone formation.
Specifically, the mature microrna excised from mir214 is predicted to target two activating. Read role of mirnas in bone and their potential as therapeutic targets, current opinion in pharmacology on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. P mir 214 targets atf4 to inhibit bone formation nat med 2012 dec 9 pmid. Since mirnas target genes and inhibit their expression, the expression pattern of a mirna and its target gene should be opposite. As bone loss is common in as, and mir 214 plays an important role in regulating bone formation, the aim of this study was to investigate the effect of mir 214, which is stimulated by il17a, on bone loss in as. Knockdown of mir 214 in contrast led to an increase in bone mineralization in mice. One study demonstrated that mir 214 targeted osterix to inhibit osteogenic differentiation in c2c12 myoblast cells. The detailed function and molecular mechanism of mir 2143p in adipocyte development is unclear. Given that the osteoclastic mir 2143p could transfer to osteoblast to inhibit bone formation. However, the diagnosis of osteoporosis and osteopenia based on measurement of bone mineral density.
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