scholarly journals Nanoparticles Delivering Antagomir-483-5p to Bone Marrow Mesenchymal Stem Cells Prevent Osteoporosis by Increasing Bone Formation

2021 ◽  
Author(s):  
Yue Zhou ◽  
Hao Jia ◽  
Aihua Hu ◽  
Rangru Liu ◽  
Xiangzhou Zeng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Small Molecules ◽  
Target Genes ◽  
Osteoblastic Differentiation ◽  
Mitogen Activated Protein Kinase ◽  
Osteoporosis Prevention ◽  
Bone Formation Markers

Abstract Background: Promoting bone marrow mesenchymal stem cell (BMSC) osteoblastic differentiation is a promising therapeutic strategy for osteoporosis (OP). The present study demonstrates that miR-483-5p inhibits the osteogenic differentiation of BMSCs. Therefore, selectively delivering the nanoparticles carrying antagomir-483-5p (miR-483-5p inhibitor) to BMSCs is expected to become an effective treatment drug for OP.Methods: Real-time PCR assays were used to analyse miR-483-5p, ALP and Bglap levels in BMSCs of ovariectomized and aged osteoporotic mice. To selectively and efficiently deliver antagomir-483-5p to BMSCs in vivo, immunoglobulin G and poloxamer-188 were used to encapsulate the functional small molecules, and BMSC-targeting aptamer was employed to confirm the direction of the nanoparticles. Luciferase assays were used to determine the target genes of miR-483-5p. Western blot assays and immunohistochemistry staining were used to detect the targets in vitro and vivo.Results: miR-483-5p levels were increased in BMSCs of ovariectomized and aged osteoporotic mice. Inhibition of miR-483-5p levels in BMSCs by antagomir-483-5p in vitro promoted the expression of bone formation markers, such as ALP and Bglap. The FAM-BMSC-aptamer-nanoparticles carrying antagomir-483-5p were taken up by BMSCs, resulting in stimulation of BMSC osteoblastic differentiation in vitro and osteoporosis prevention in vivo. Furthermore, our research demonstrated that mitogen-activated protein kinase 1 (MAPK1) and SMAD family member 5 (Smad5) were direct targets of miR-483-5p in regulating BMSC osteoblastic differentiation and osteoporosis pathological processes. Conclusions: The important therapeutic role of FAM-BMSC-aptamer-nanoparticles carrying antagomir-483-5p in osteoporosis was established in our study. These nanoparticles are novel candidate for the clinical prevention and treatment of osteoporosis. The optimized targeted drug delivery platform for small molecules will provide new ideas for the treatment of clinical diseases.

4:51146. Nell-1 Induces Osteoblastic Differentiation of Bone Marrow Mesenchymal Cells In Vitro and Bone Formation In Vivo

2006 ◽  
Vol 6 (5) ◽  
pp. 74S
Author(s):  
Tara Aghaloo ◽  
Xinquan Jiang ◽  
Xinli Zhang ◽  
Zhang Zhiyuang ◽  
Jeffrey C. Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Osteoblastic Differentiation ◽  
Mesenchymal Cells ◽  
Bone Marrow Mesenchymal Cells

scholarly journals Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells

2009 ◽  
Vol 185 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Guizhong Liu ◽  
Sapna Vijayakumar ◽  
Luca Grumolato ◽  
Randy Arroyave ◽  
HuiFang Qiao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Wnt Signaling ◽  
De Novo ◽  
Human Mesenchymal Stem Cells ◽  
Mitogen Activated Protein Kinase ◽  
Bone Homeostasis

Genetic evidence indicates that Wnt signaling is critically involved in bone homeostasis. In this study, we investigated the functions of canonical Wnts on differentiation of adult multipotent human mesenchymal stem cells (hMSCs) in vitro and in vivo. We observe differential sensitivities of hMSCs to Wnt inhibition of osteogenesis versus adipogenesis, which favors osteoblastic commitment under binary in vitro differentiation conditions. Wnt inhibition of osteogenesis is associated with decreased expression of osteoblastic transcription factors and inhibition of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation, which are involved in osteogenic differentiation. An hMSC subpopulation exhibits high endogenous Wnt signaling, the inhibition of which enhances osteogenic and adipogenic differentiation in vitro. In an in vivo bone formation model, high levels of Wnt signaling inhibit de novo bone formation by hMSCs. However, hMSCs with exogenous expression of Wnt1 but not stabilized β-catenin markedly stimulate bone formation by naive hMSCs, arguing for an important role of a canonical Wnt gradient in hMSC osteogenesis in vivo.

Prospective In Vivo Identification of Osteogenic Stem/Progenitor Cells from Bone Marrow-Derived Lin−/Sca-1+/CD45− Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1409-1409
Author(s):  
Zhuo Wang ◽  
Junghun Jung ◽  
Magdalena Kucia ◽  
Junhui Song ◽  
Yusuke Shiozawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Formation ◽  
Cultured Cells ◽  
Fluorescent Microscopy ◽  
Micro Ct ◽  
Mineralized Tissue

Abstract We previously developed an in vivo prospective assay for identification of non-cultured cells with MSC potential. Using this assay we identified a population of cells that were slowly cycling and of low density that were capable of multilineage differentiation both in vitro and in vivo (Z. Wang et al, Stem Cells. 2006 24(6):1573). Further characterization of these cells suggested that they resemble a homogenous population of rare Lin−/Sca-1+/CD45− cells that have the morphology and express several markers of undifferentiated embryonic-like stem cells. In vitro the Lin−/Sca-1+/CD45− cells may differentiate into cells from all three germ-layers (M. Kucia et al, Leukemia. 2007 21(2):297). To determine the in vivo fate of this population, we transplanted 500 or 5,000 Lin−/Sca-1+/CD45− cells from a GFP mouse into SCID mice in each group (n=3) immediately after cell sorting to evaluate tissue generation in vivo. At 4 weeks the regenerative potential of these populations was evaluated by micro-CT and histology, and cells were tracked by gross examination of the harvested tissues by fluorescent microscopy. The results showed that a large number of GFP+ cells are located in the implants, indicating that the transplanted cells maintain the ability to contribute to the generation of new tissue. Bone-like tissue was observed in the Lin−/Sca-1+/CD45− group with as low as 500-cells/implant, while 5,000 Lin−/Sca-1+/CD45− cells generated significantly larger mineralized tissue volume, which was confirmed by micro-CT. Lin−/Sca-1+/CD45+ cell only implantation did not form any mineralized tissue, however, while mixed with 2x106 whole bone morrow cells, positive mineralized tissue occurred. Whole bone marrow mixture also improve bone formation in Lin−/Sca-1+/CD45− cell implants compared the actual bone volumes measured by micro-CT. This study demonstrates that non-cultured BM-derived Lin−/Sca-1+/CD45− cells exhibit the capacity to form bone in vivo with as low as 500 cells/implant. Whole bone marrow mixtures can enhance the bone formation, presumably through the interaction of other populations cells. Based on these findings, it is proposed that non-cultured BM-derived Lin−/Sca-1+/CD45− cells are enriched osteogenic cells that can be applied to bone regeneration in vivo.

Effects of in vitro chondrogenic priming time of bone-marrow-derived mesenchymal stromal cells on in vivo endochondral bone formation

2015 ◽  
Vol 13 ◽  
pp. 254-265 ◽  
Author(s):  
Wanxun Yang ◽  
Sanne K. Both ◽  
Gerjo J.V.M. van Osch ◽  
Yining Wang ◽  
John A. Jansen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Endochondral Bone Formation ◽  
Endochondral Bone

STIMULATION OF BONE MARROW CELLS AND BONE FORMATION BY NACRE. IN VIVO AND IN VITRO STUDIES

Bioceramics ◽  
1999 ◽  
Author(s):  
M. Lamghari ◽  
S. Berland ◽  
A. Laurent ◽  
H. Huet ◽  
M.J. Almeida ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Marrow Cells ◽  
In Vitro Studies ◽  
Stimulation Of ◽  
Marrow Cells

scholarly journals Porcine Collagen–Bone Composite Induced Osteoblast Differentiation and Bone Regeneration In Vitro and In Vivo

Polymers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 93 ◽  
Author(s):  
Eisner Salamanca ◽  
Chia Chen Hsu ◽  
Wan Ling Yao ◽  
Cheuk Sing Choy ◽  
Yu Hwa Pan ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Osteoblast Differentiation ◽  
Critical Size ◽  
Guided Bone Regeneration ◽  
Autogenous Bone ◽  
Critical Size Defects ◽  
Bone Formation Markers

Due to autogenous bone limitations, some substitute bone grafts were developed. Collagenated porcine graft (CPG) is able to regenerate new bone, although the number of studies is insufficient, highlighting the need for future studies to better understand the biomaterial. In order to understand better CPG′s possible dental guided bone regeneration indications, the aim of this work was to determine CPG′s biological capacity to induce osteoblast differentiation in vitro and guided bone regeneration in vivo, whilst being compared with commercial hydroxyapatite and beta tricalcium phosphate (HA/β-TCP) and porcine graft alone. Cell cytotoxicity (WST-1), alkaline phosphatase activity (ALP), and real-time polymerase chain reaction (qPCR) were assessed in vitro. Critical size defects of New Zealand white rabbits were used for the in vivo part, with critical size defect closures and histological analyses. WST-1 and ALP indicated that CPG directly stimulated a greater proliferation and confluency of cells with osteoblastic differentiation in vitro. Gene sequencing indicated stable bone formation markers, decreased resorption makers, and bone remodeling coupling factors, making the transition from osteoclast to osteoblast expression at the end of seven days. CPG resulted in the highest new bone regeneration by osteoconduction in critical size defects of rabbit calvaria at eight weeks. Nonetheless, all biomaterials achieved nearly complete calvaria defect closure. CPG was found to be osteoconductive, like porcine graft and HA/β-TCP, but with higher new bone formation in critical size defects of rabbit calvaria at eight weeks. CPG can be used for different dental guided bone regeneration procedures; however, further studies are necessary.

Abstract WMP44: Mir-145 Mediates Bone-marrow-stromal Cell Derived From Type-one Diabetes (t1dm) Rats Induced Neurorestorative Effects in T1dm Rats

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Chengcheng Cui ◽  
Michael Chopp ◽  
Xinchun Ye ◽  
Alex Zacharek ◽  
Ruizhou Ning ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cortical Neurons ◽  
Target Genes ◽  
Capillary Tube ◽  
Border Zone ◽  
Therapeutic Effects ◽  
Ischemic Brain ◽  
Type One Diabetes

Objective: Treatment of stroke with bone-marrow-stromal cells (BMSCs) derived from type-one diabetes (T1DM) rats (DM-BMSCs) improves functional recovery compared to BMSCs derived from normal rats (Nor-BMSCs) and non treatment T1DM rats. In the study, we tested the mechanisms underlying the benefit of the treatment of T1DM stroke with DM-BMSCs. Methods: T1DM rats induced by streptozocin in male Wistar rats were subjected to 2h middle cerebral artery occlusion (MCAo) and were treated at 24h after MCAo via tail vein with: 1) vehicle control; 2) DM-BMSCs; 3) DM-BMSCs with miR-145 overexpression (miR-145+/+DM-BMSCs)(5x10^6) (n=8/group). A battery of functional tests, vascular,white matter (WM) measurements, and cell culture experiments were performed. Results: In vitro, DM-BMSCs exhibited reduced level of miR-145, and increased survival rate compared to Nor-BMSCs. miR-145+/+DM-BMSCs significantly decreased DM-BMSCs survival. DM-BMSCs media increased capillary tube formation and axonal outgrowth in cultured primary cortical neurons (PCNs) compared to Nor-BMSCs media. While miR-145+/+DM-BMSCs exhibited reverse effects compared to DM-BMSCs media. In vivo, DM-BMSCs improved functional outcome, vascular and WM remodeling in the ischemic border zone (IBZ) compared to T1DM-MCAo rats. However, miR-145+/+DM-BMSCs significantly attenuated DM-BMSCs induced beneficial effects. To further test the underlying mechanism of miR-145 mediated DM-BMSCs induced therapeutic effects in T1DM stroke rats, miR-145 target genes adenosine triphosphate-binding cassette transporter 1 (ABCA1) and insulin-like growth factor 1 receptor (IGFR-1) were measured in IBZ. ABCA1 and IGFR1 have neurorestorative effects. Reduction of IGF1 contributes ABCA1 deficiency induced damage in ischemic brain. We found that DM-BMSCs significantly decreased miR-145, increased ABCA1 and IGFR-1 expression in IBZ compared to Nor-BMSCs. While miR-145+/+DM-BMSCs significantly decreased ABCA1 and IGFR-1 expression in IBZ. Conclusion: DM-BMSCs exhibit decreased miR-145 expression and increase miR-145 target gene ABCA1 and IGFR-1 expression in ischemic brain. The miR-145/ABCA1/IGFR-1 pathway may contribute to DM-BMSCs induced neurorestorative effects in T1DM stroke.

scholarly journals Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro

2001 ◽  
Vol 168 (1) ◽  
pp. 131-139 ◽  
Author(s):  
S Keila ◽  
A Kelner ◽  
M Weinreb
Keyword(s):  
Bone Marrow ◽  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Nodule Formation ◽  
Anabolic Effect ◽  
Aging Rats ◽  
Old Rats

Prostaglandin E(2) (PGE(2)) has been shown to exert a bone anabolic effect in young and adult rats. In this study we tested whether it possesses a similar effect on bone formation and bone mass in aging rats. Fifteen-month-old rats were injected daily with either PGE(2) at 5 mg/kg or vehicle for 14 days. PGE(2) treatment stimulated the rate of cancellous bone formation (a approximately 5.5-fold increase in bone formation rate), measured by the incorporation of calcein into bone-forming surfaces at the tibial proximal metaphysis. This effect resulted in increased cancellous bone area (+54%) at the same site. Since PGE(2) treatment resulted in a much higher proportion of bone surface undergoing bone formation and thus lined with osteoblasts, we tested the hypothesis that PGE(2) stimulates osteoblast differentiation from bone marrow precursor cells both in vivo and in vitro. We found that ex vivo cultures of bone marrow stromal cells from rats injected for 2 weeks with PGE(2) at 5 mg/kg per day yielded more ( approximately 4-fold) mineralized nodules and exhibited a greater (by 30-40%) alkaline phosphatase activity compared with cultures from vehicle-injected rats, attesting to a stimulation of osteoblastic differentiation by PGE(2). We also compared the osteogenic capacity of bone marrow from aging (15-month-old) versus young (5-week-old) rats and its regulation by PGE(2) in vitro. Bone marrow stromal cell cultures from aging rats exhibited a greatly diminished osteogenic capacity, reflected in reduced nodule formation ( approximately 6% of young animals) and lower alkaline phosphatase activity ( approximately 60% of young animals). However, these parameters could be stimulated in both groups of animals by incubation with 10-100 nM PGE(2). The magnitude of this stimulation was greater in cultures from aging rats (+550% vs +70% in nodule formation of aging compared with young rats). In conclusion, we demonstrate here that PGE(2) exerts a bone anabolic effect in aging rats, similar to the effect we and others have reported in young, growing rats. The PGE(2)-stimulated bone formation, which augments bone mass, most likely results from recruitment of osteoblasts from their bone marrow stromal precursors.

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