Long non-coding RNA MIR22HG promotes osteogenic differentiation of bone marrow mesenchymal stem cells via PTEN/ AKT pathway

Abstract Osteoporosis is a prevalent metabolic bone disease characterized by low bone mineral density and degenerative disorders of bone tissues. Previous studies showed the abnormal osteogenic differentiation of endogenous bone marrow mesenchymal stem cells (BMSCs) contributes to the development of osteoporosis. However, the underlying mechanisms by which BMSCs undergo osteogenic differentiation remain largely unexplored. Recently, long non-coding RNAs have been discovered to play important roles in regulating BMSC osteogenesis. In this study, we first showed MIR22HG, which has been demonstrated to be involved in the progression of several cancer types, played an important role in regulating BMSC osteogenesis. We found the expression of MIR22HG was significantly decreased in mouse BMSCs from the osteoporotic mice and it was upregulated during the osteogenic differentiation of human BMSCs. Overexpression of MIR22HG in human BMSCs enhanced osteogenic differentiation, whereas MIR22HG knockdown inhibited osteogenic differentiation both in vitro and in vivo. Mechanistically, MIR22HG promoted osteogenic differentiation by downregulating phosphatase and tensin homolog (PTEN) and therefore activating AKT signaling. Moreover, we found MIR22HG overexpression promoted osteoclastogenesis of RAW264.7 cells, which indicated that MIR22HG played a significant role in bone metabolism and could be a therapeutic target for osteoporosis and other bone-related diseases.

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The osteogenic differentiation of dog bone marrow mesenchymal stem cells in a thermo-sensitive injectable chitosan/collagen/β-glycerophosphate hydrogel: in vitro and in vivo

Journal of Materials Science Materials in Medicine ◽

10.1007/s10856-011-4386-4 ◽

2011 ◽

Vol 22 (9) ◽

pp. 2111-2118 ◽

Cited By ~ 39

Author(s):

Bin Sun ◽

Wei Ma ◽

Fang Su ◽

Yi Wang ◽

Jiaqiang Liu ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Dog Bone ◽

Marrow Mesenchymal Stem Cells

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Tilianin Promotes the Proliferation and Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.20:259-264 ◽

2021 ◽

Vol 20 (2) ◽

pp. 259-264

Author(s):

Zhixing Xue ◽

Jin Yang ◽

Panfeng Yu

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

High Glucose ◽

Flavonoid Glycoside ◽

Mineral Density ◽

Treatment Of Osteoporosis ◽

Marrow Mesenchymal Stem Cells

Osteoporosis is a systemic bone disease characterized by a decrease in bone mineral density and mass. To examine the mechanism(s) underlying the pathogenesis of osteoporosis, we have used an in vitro model of osteoporosis induced by exposure to high glucose. Tilianin is a flavonoid glycoside isolated from Dracocephalum moldavica L. that has been reported to exhibit a variety of pharmacologic activities. However, the utility of tilianin in the treatment of osteoporosis remains unexplored. To this end, we have examined the effect of tilianin on bone marrow mesenchymal stem cells exposed to high glucose. Our data revealed that tilianin suppressed apoptosis, promoted osteogenic differentiation, and survival of the bone marrow mesenchymal stem cells in the presence of high glucose. Our data therefore confirmed that tilianin could serve as a promising drug for the treatment of osteoporosis.

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Recombinant human BMP-2 accelerates the migration of bone marrow mesenchymal stem cells via the CDC42/PAK1/LIMK1 pathway in vitro and in vivo

Biomaterials Science ◽

10.1039/c8bm00846a ◽

2019 ◽

Vol 7 (1) ◽

pp. 362-372 ◽

Cited By ~ 6

Author(s):

Shuhao Liu ◽

Yang Liu ◽

Libo Jiang ◽

Zheng Li ◽

Soomin Lee ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Marrow Mesenchymal Stem Cells

BMP-2-induced migration of BMSCs can be inhibited by silencing CDC42 in vitro and in vivo.

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Melatonin Inhibits the Ferroptotic Pathway in Rat Bone Marrow Mesenchymal Stem Cells by Activating the PI3K-AKT-mTOR Signaling Axis to Attenuate Steroid-induced Osteoporosis

10.21203/rs.3.rs-850531/v1 ◽

2021 ◽

Author(s):

meng li ◽

ning yang ◽

li hao ◽

wei zhou ◽

lei li ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

High Dose ◽

Treatment Pathways ◽

Marrow Mesenchymal Stem Cells

Abstract ObjectivesSteroid-induced osteoporosis (SIOP) is a secondary osteoporosis, which is a systemic bone disease characterized by low bone mass, bone microstructure damage, increased bone fragility, and easy fracture. However, the specific mechanism remains unclear. Glucocorticoid-induced death of osteoblasts and bone marrow mesenchymal stem cells (BMSCs) is an important factor in SIOP. Ferroptosis is an iron-dependent programmed cell death that differs from apoptosis, cell necrosis, and autophagy, which can be induced by many factors. Herein, we aimed to explore whether glucocorticoids (GCs) cause ferroptosis in BMSCs and determine possible treatment pathways and mechanisms of action. Melatonin (MT), a hormone secreted by the pineal gland, displays strong antioxidant abilities to scavenge free radicals and alleviates ferroptosis in many tissues and organs. MethodsIn this study, we used high-dose dexamethasone (DEX) to observe whether glucocorticoids induced ferroptosis in BMSCs. We then assessed whether MT can inhibit the ferroptotic pathway, thereby providing early protection against GC-induced SIOP, and investigated the signaling pathways involved.ResultsIn vitro experiments showed that MT intervention significantly improved GC-induced ferroptosis in BMSCs and significantly improved SIOP in vivo. Pathway analysis showed that MT improves ferroptosis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis. MT upregulates expression of PI3K, which is an important regulator of ferroptosis resistance. PI3K activators mimic the anti-ferroptosis effect of MT, but after blocking the PI3K pathway, the effect of MT is weakened. Obviously, MT can protect against SIOP induced by GC. Notably, even after GC-induced ferroptosis begins, MT can confer protection against SIOP. ConclusionOur research confirms that GC-induced ferroptosis is closely related to SIOP. Melatonin can inhibit ferroptosis by activating the PI3K-AKT-mTOR signaling pathway, thereby reducing the occurrence of steroid-induced osteoporosis. Therefore, MT may provide a novel strategy for preventing and treating SIOP.

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Progranulin Promotes Osteogenic Differentiation and Osteosynthesis of Bone Marrow Mesenchymal Stem Cells and Alleviates Osteoporosis Through Phosphatidylinositol 3-Kinase/Protein Kinase B/Peroxisome Proliferator-Activated Receptor γ Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2493 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1865-1870

Author(s):

Yang Ying ◽

Binghao Zhao ◽

Wei Qian ◽

Li Xu

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Mrna Level ◽

Control Group ◽

Peroxisome Proliferator ◽

Mineral Density ◽

Alp Activity ◽

Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) have self-renewal potential with multi-directional differentiation. Progranulin prevents bone degradation, inhibits inflammation and protects bone tissue. However, the role of Progranulin in osteoporotic BMSCs is unclear. Osteoporosis (OP) rat models were prepared by ovarian removal and treated with different doses (5 and 10 μM) of Progranulin followed by analysis of BMP-2 level by ELISA, bone mineral density and ALP activity. OP rat BMSCs were isolated and assigned into control group and Progranulin group followed by analysis of Progranulin level by ELISA, cell proliferation by MTT assay, RUNX2 and COL1A1 mRNA level by Real time PCR, and PI3K/Akt/PPARγ signaling protein level by Western blot. Progranulin treatment of OP rats dose-dependently increased BMP-2 expression, bone density and ALP activity. Compared with OP group, there were significant differences (P <0.05). Progranulin expression and BMSCs proliferation was increased, and RUNX2 and COL1A1 mRNA expression was elevated in Progranulin-treated OP group along with increased PI3K/Akt expression and decreased PPARγ protein expression. Compared with OP group, the difference was statistically significant, and the change was more significant with increasing concentration (P <0.05). Progranulin promotes BMSCs osteogenic differentiation and proliferation by regulating PI3K/Akt/PPARγ signaling pathway, which is beneficial for OP rats’ bone synthesis.

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The negatively charged microenvironment of collagen hydrogels regulates the chondrogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo

Journal of Materials Chemistry B ◽

10.1039/d0tb00172d ◽

2020 ◽

Vol 8 (21) ◽

pp. 4680-4693

Author(s):

Jirong Yang ◽

Yumei Xiao ◽

Zizhao Tang ◽

Zhaocong Luo ◽

Dongxiao Li ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Protein Adsorption ◽

Cell Morphology ◽

Chondrogenic Differentiation ◽

Collagen Hydrogels ◽

Marrow Mesenchymal Stem Cells

The different negatively charged microenvironments of collagen hydrogels affect the protein adsorption, cell morphology, and chondrogenic differentiation of BMSCs in vitro and in vivo.

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Kartogenin enhances the therapeutic effect of bone marrow mesenchymal stem cells derived exosomes in cartilage repair

Nanomedicine ◽

10.2217/nnm-2019-0208 ◽

2020 ◽

Vol 15 (3) ◽

pp. 273-288 ◽

Cited By ~ 1

Author(s):

Chun Liu ◽

Yun Li ◽

Zhijian Yang ◽

Zhiyou Zhou ◽

Zhihao Lou ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Therapeutic Effect ◽

Bone Marrow Mscs ◽

In Vivo Experiments ◽

Marrow Mesenchymal Stem Cells ◽

Cartilage Diseases

The effectiveness of mesenchymal stem cells (MSC) in the treatment of cartilage diseases has been demonstrated to be attributed to the paracrine mechanisms, especially the mediation of exosomes. But the exosomes derived from unsynchronized MSCs may be nonhomogeneous and the therapeutic effect varies between samples. Aim: To produce homogeneous and more effective exosomes for the regeneration of cartilage. Materials & methods: In this study we produced specific exosomes from bone marrow MSCs (BMSC) through kartogenin (KGN) preconditioning and investigated their performance in either in vitro or in vivo experiments. Results & conclusion: The exosomes derived from KGN-preconditioned BMSCs (KGN-BMSC-Exos) performed more effectively than the exosomes derived from BMSCs (BMSC-Exos). KGN preconditioning endowed BMSC-Exos with stronger chondral matrix formation and less degradation.

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Nanocomposite scaffolds composed of Apacite (apatite-calcite) nanostructures, poly (ε-caprolactone) and poly (2-hydroxyethylmethacrylate): The effect of nanostructures on physico-mechanical properties and osteogenic differentiation of human bone marrow mesenchymal stem cells in vitro

Materials Science and Engineering C ◽

10.1016/j.msec.2020.111271 ◽

2020 ◽

Vol 117 ◽

pp. 111271

Author(s):

Mehdi Shams ◽

Mohammad Karimi ◽

Masoomeh Heydari ◽

Ali Salimi

Keyword(s):

Mechanical Properties ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Human Bone ◽

Human Bone Marrow ◽

Marrow Mesenchymal Stem Cells ◽

Nanocomposite Scaffolds

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Acceleration of Bone Regeneration in Critical-Size Defect Using BMP-9-Loaded nHA/ColI/MWCNTs Scaffolds Seeded with Bone Marrow Mesenchymal Stem Cells

BioMed Research International ◽

10.1155/2019/7343957 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Ran Zhang ◽

Xuewen Li ◽

Yao Liu ◽

Xiaobo Gao ◽

Tong Zhu ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Composite Scaffold ◽

Marrow Mesenchymal Stem Cells

Biocompatible scaffolding materials play an important role in bone tissue engineering. This study sought to develop and characterize a nano-hydroxyapatite (nHA)/collagen I (ColI)/multi-walled carbon nanotube (MWCNT) composite scaffold loaded with recombinant bone morphogenetic protein-9 (BMP-9) for bone tissue engineering by in vitro and in vivo experiments. The composite nHA/ColI/MWCNT scaffolds were fabricated at various concentrations of MWCNTs (0.5, 1, and 1.5% wt) by blending and freeze drying. The porosity, swelling rate, water absorption rate, mechanical properties, and biocompatibility of scaffolds were measured. After loading with BMP-9, bone marrow mesenchymal stem cells (BMMSCs) were seeded to evaluate their characteristics in vitro and in a critical sized defect in Sprague-Dawley rats in vivo. It was shown that the 1% MWCNT group was the most suitable for bone tissue engineering. Our results demonstrated that scaffolds loaded with BMP-9 promoted differentiation of BMMSCs into osteoblasts in vitro and induced more bone formation in vivo. To conclude, nHA/ColI/MWCNT scaffolds loaded with BMP-9 possess high biocompatibility and osteogenesis and are a good candidate for use in bone tissue engineering.

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