scholarly journals Osteoprotegerin reduces osteoclast resorption activity without affecting osteogenesis on nanoparticulate mineralized collagen scaffolds

2019 ◽  
Vol 5 (6) ◽  
pp. eaaw4991 ◽  
Author(s):  
Xiaoyan Ren ◽  
Qi Zhou ◽  
David Foulad ◽  
Aleczandria S. Tiffany ◽  
Marley J. Dewey ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Direct Contact ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Collagen Scaffolds ◽  
Decoy Receptor ◽  
Osteoclast Resorption ◽  
Mineralized Collagen

The instructive capabilities of extracellular matrix–inspired materials for osteoprogenitor differentiation have sparked interest in understanding modulation of other cell types within the bone regenerative microenvironment. We previously demonstrated that nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) scaffolds efficiently induced osteoprogenitor differentiation and bone healing. In this work, we combined adenovirus-mediated delivery of osteoprotegerin (AdOPG), an endogenous anti-osteoclastogenic decoy receptor, in primary human mesenchymal stem cells (hMSCs) with MC-GAG to understand the role of osteoclast inactivation in augmentation of bone regeneration. Simultaneous differentiation of osteoprogenitors on MC-GAG and osteoclast progenitors resulted in bidirectional positive regulation. AdOPG expression did not affect osteogenic differentiation alone. In the presence of both cell types, AdOPG-transduced hMSCs on MC-GAG diminished osteoclast-mediated resorption in direct contact; however, osteoclast-mediated augmentation of osteogenic differentiation was unaffected. Thus, the combination of OPG with MC-GAG may represent a method for uncoupling osteogenic and osteoclastogenic differentiation to augment bone regeneration.

scholarly journals Involvement of the long noncoding RNA H19 in osteogenic differentiation and bone regeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zimo Zhou ◽  
Mohammad Showkat Hossain ◽  
Da Liu
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Osteoblast Differentiation ◽  
Osteoclast Differentiation ◽  
Complex Processes ◽  
Osteogenic Induction ◽  
Novel Target

AbstractOsteogenic differentiation and bone regeneration are complex processes involving multiple genes and multiple steps. In this review, we summarize the effects of the long noncoding RNA (lncRNA) H19 on osteogenic differentiation.Osteogenic differentiation includes matrix secretion and calcium mineralization as hallmarks of osteoblast differentiation and the absorption of calcium and phosphorus as hallmarks of osteoclast differentiation. Mesenchymal stem cells (MSCs) form osteoprogenitor cells, pre-osteoblasts, mature osteoblasts, and osteocytes through induction and differentiation. lncRNAs regulate the expression of coding genes and play essential roles in osteogenic differentiation and bone regeneration. The lncRNA H19 is known to have vital roles in osteogenic induction.This review highlights the role of H19 as a novel target for osteogenic differentiation and the promotion of bone regeneration.

scholarly journals The role of hesperetin on osteogenesis of human mesenchymal stem cells and its function in bone regeneration

Oncotarget ◽  
2017 ◽  
Vol 8 (13) ◽  
pp. 21031-21043 ◽  
Author(s):  
Deting Xue ◽  
Erman Chen ◽  
Wei Zhang ◽  
Xiang Gao ◽  
Shengdong Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Human Mesenchymal Stem Cells

scholarly journals Repair of critical-size porcine craniofacial bone defects using a collagen-polycaprolactone composite biomaterial

2021 ◽  
Author(s):  
Marley J Dewey ◽  
Derek J Milner ◽  
Daniel Weisgerber ◽  
Colleen Flanagan ◽  
Marcello Rubessa ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Fibrous Tissue ◽  
Bone Defects ◽  
Large Animal ◽  
Collagen Scaffolds ◽  
Shape Fitting ◽  
Large Animal Models ◽  
3D Printed ◽  
Mineralized Collagen

Regenerative medicine approaches for massive craniomaxillofacial bone defects face challenges associated with the scale of missing bone, the need for rapid graft-defect integration, and challenges related to inflammation and infection. Mineralized collagen scaffolds have been shown to promote mesenchymal stem cell osteogenesis due to their porous nature and material properties, but are mechanically weak, limiting surgical practicality. Previously, these scaffolds were combined with 3D-printed polycaprolactone mesh to form a scaffold-mesh composite to increase strength and promote bone formation in sub-critical sized porcine ramus defects. Here, we compare the performance of mineralized collagen-polycaprolactone composites to the polycaprolactone mesh in a critical-sized porcine ramus defect model. While there were no differences in overall healing response between groups, our data demonstrated broadly variable metrics of healing regarding new bone infiltration and fibrous tissue formation. Abscesses were present surrounding some implants and polycaprolactone polymer was still present after 9-10 months of implantation. Overall, while there was limited successful healing, with 2 of 22 implants showed substantial levels of bone regeneration, and others demonstrating some form of new bone formation, the results suggest targeted improvements to improve repair of large animal models to more accurately represent craniomaxillofacial bone healing. Notably, strategies to increase osteogenesis throughout the implant, modulate the immune system to support repair, and employ shape-fitting tactics to avoid implant micromotion and resultant fibrosis. Improvements to the mineralized collagen scaffolds involve changes in pore size and shape to increase cell migration and osteogenesis and inclusion or delivery of factors to aid vascular ingrowth and bone regeneration.

scholarly journals Induction of Proteases in Peritoneal Carcinomatosis, the Role of ICAM-1/CD43 Interaction

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Nawar A. Alkhamesi ◽  
Gretta Roberts ◽  
Paul Ziprin ◽  
David H. Peck ◽  
Ara W. Darzi
Keyword(s):  
Tumor Cells ◽  
Tumor Invasion ◽  
Direct Contact ◽  
Therapeutic Option ◽  
Gelatin Zymography ◽  
Cell Types ◽  
Vital Role ◽  
Indirect Contact ◽  
Clinical Issue

Introduction The development of peritoneal metastases is a significant clinical issue in the treatment of abdominal cancers and is associated with poor prognosis. We have previously shown that ICAM-1-CD43 interaction plays a significant role in tumor adhesion. However, an invasive phenotype is critical to establish tumor progression via cell associated and secreted proteases including matrix metalloproteinases. High metalloproteinases level significantly enhanced metastasis phenotype on tumors, a detrimental effect on surgical outcome. We investigated the role of direct and indirect signaling between the mesothelium and the tumor cells in enhancing tumor invasion and possible therapeutic intervention. Methods Mesothelial cells were enzymatically derived from human omental tissue and implanted in 24 wells plates. Colorectal cancer cells were then introduced and allowed a direct and an indirect contact with the mesothelial layer. Anti-ICAM antibodies, anti-CD43 antibodies, and heparin were used to block MMP production. Gelatin zymography was performed on the supernatant to detect MMPs activity. Results MMP production was observed in mesothelial and tumor cells. Direct contact between cell types enhanced MMP9 and 2 (p < 0.05). Indirect contact also stimulate MMPs but at a lower degree. ICAM-1 blocking antibodies attenuated MMP production in direct contact to that observed in the indirect. Heparin introduction achieved a similar outcome. Conclusions ICAM-1-CD43 interaction plays a vital role in tumor cells-peritoneum adhesion and invasion, which is manifested by the increased production of MMPs leading to tumor invasion and peritoneal loco-regional. Blocking this interaction with heparin can provide a new therapeutic option.

scholarly journals Mineralized collagen scaffolds fabricated with amniotic membrane matrix increase osteogenesis under inflammatory conditions

2020 ◽  
Author(s):  
Marley J. Dewey ◽  
Eileen M. Johnson ◽  
Simona T. Slater ◽  
Derek J. Milner ◽  
Matthew B. Wheeler ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Amniotic Membrane ◽  
Bone Repair ◽  
Composite Scaffold ◽  
High Energy ◽  
Collagen Scaffolds ◽  
Membrane Matrix ◽  
Inflammatory Conditions ◽  
Mineral Deposition ◽  
Mineralized Collagen

ABSTRACTDefects in craniofacial bones occur congenitally, after high-energy impacts, and during the course of treatment for stroke and cancer. These injuries are difficult to heal due to the overwhelming size of the injury area and the inflammatory environment surrounding the injury. Significant inflammatory response after injury may greatly inhibit regenerative healing. We have developed mineralized collagen scaffolds that can induce osteogenic differentiation and matrix biosynthesis in the absence of osteogenic media or supplemental proteins. The amniotic membrane is derived from placentas and has been recently investigated as an extracellular matrix to prevent chronic inflammation. Herein, we hypothesized that a mineralized collagen-amnion composite scaffold could increase osteogenic activity in the presence of inflammatory cytokines. We report mechanical properties of a mineralized collagen-amnion scaffold and investigated osteogenic differentiation and mineral deposition of porcine adipose derived stem cells within these scaffolds as a function of inflammatory challenge. Incorporation of amniotic membrane matrix promotes osteogenesis similarly to un-modified mineralized collagen scaffolds, and increases in mineralized collagen-amnion scaffolds under inflammatory challenge. Together, these findings suggest that a mineralized collagen-amnion scaffold may provide a beneficial environment to aid craniomaxillofacial bone repair, especially in the course of defects presenting significant inflammatory complications.

scholarly journals MiR-144-5p, an exosomal miRNA from bone marrow-derived macrophage in type 2 diabetes, impairs bone fracture healing via targeting Smad1

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dong Zhang ◽  
Yifan Wu ◽  
Zonghuan Li ◽  
Hairen Chen ◽  
Siyuan Huang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Fracture Healing ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Fracture Repair ◽  
Osteogenic Potential ◽  
Patients With Diabetes ◽  
The Impact

Abstract Background Patients with diabetes have an increased risk of nonunion and delayed union of fractures. Macrophages have been shown as a key player in diabetic complications. However, it remains obscure how diabetic milieu affects macrophage-derived exosomes and its implications on osteogenic differentiation of BMSCs. In this study, we aim to define the impact of diabetic milieu on macrophage-derived exosomes, role of extracellular vesicles in intercellular communication with BMSCs, and subsequent effects on osteogenic differentiation and fracture repair. Results The osteogenic potential and the ability of fracture repair of exosomes derived from diabetic bone marrow-derived macrophages (dBMDM-exos) were revealed to be lower, as compared with non-diabetic bone marrow-derived macrophages (nBMDM-exos) in vitro and in vivo. Interestingly, miR-144-5p levels were sharply elevated in dBMDM-exos and it could be transferred into BMSCs to regulate bone regeneration by targeting Smad1. In addition, the adverse effects of dBMDM-exos on the osteogenic potential and the ability of fracture repair were reversed through the suppression of miR-144-5p inhibition in vitro and vivo. Conclusions The results demonstrated an important role of exosomal miR-144-5p in bone regeneration, offering insight into developing new strategy for the improvement of fracture healing in patients with diabetes mellitus. Graphic Abstract

scholarly journals Role of Wnt11 during Osteogenic Differentiation of Human Mesenchymal Stem Cells on Microstructured Titanium Surfaces

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Barbara D. Boyan ◽  
Rene Olivares-Navarrete ◽  
Michael B. Berger ◽  
Sharon L. Hyzy ◽  
Zvi Schwartz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Titanium Surfaces

scholarly journals In Vitro and In Vivo Evaluation of Commercially Available Fibrin Gel as a Carrier of Alendronate for Bone Tissue Engineering

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Beom Su Kim ◽  
Feride Shkembi ◽  
Jun Lee
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Release Kinetics ◽  
Human Mesenchymal Stem Cells ◽  
Calvarial Defect ◽  
Defect Model ◽  
Fibrin Gel ◽  
In Vivo Evaluation

Alendronate (ALN) is a bisphosphonate drug that is widely used for the treatment of osteoporosis. Furthermore, local delivery of ALN has the potential to improve the bone regeneration. This study was designed to investigate an ALN-containing fibrin (fibrin/ALN) gel and evaluate the effect of this gel on both in vitro cellular behavior using human mesenchymal stem cells (hMSCs) and in vivo bone regenerative capacity. Fibrin hydrogels were fabricated using various ALN concentrations (10−7–10−4 M) with fibrin glue and the morphology, mechanical properties, and ALN release kinetics were characterized. Proliferation and osteogenic differentiation of and cytotoxicity in fibrin/ALN gel-embedded hMSCs were examined. In vivo bone formation was evaluated using a rabbit calvarial defect model. The fabricated fibrin/ALN gel was transparent with Young’s modulus of ~13 kPa, and these properties were not affected by ALN concentration. The in vitro studies showed sustained release of ALN from the fibrin gel and revealed that hMSCs cultured in fibrin/ALN gel showed significantly increased proliferation and osteogenic differentiation. In addition, microcomputed tomography and histological analysis revealed that the newly formed bone was significantly enhanced by implantation of fibrin/ALN gel in a calvarial defect model. These results suggest that fibrin/ALN has the potential to improve bone regeneration.

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