scholarly journals Peptide drugs accelerate BMP‐2‐induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling

BioEssays ◽  
2016 ◽  
Vol 38 (8) ◽  
pp. 717-725 ◽  
Author(s):  
Yasutaka Sugamori ◽  
Setsuko Mise‐Omata ◽  
Chizuko Maeda ◽  
Shigeki Aoki ◽  
Yasuhiko Tabata ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Osteoblast Differentiation ◽  
Peptide Drugs ◽  
Calvarial Bone ◽  
Mtorc1 Signaling ◽  
Stimulate Osteoblast Differentiation

In vivo Evaluation of a Collagen Scaffold Preconditioned with Adipose-derived Mesenchymal Stem Cells Used for Bone Regeneration A histological study

2018 ◽  
Vol 55 (4) ◽  
pp. 691-695
Author(s):  
Tudor Sorin Pop ◽  
Anca Maria Pop ◽  
Alina Dia Trambitas Miron ◽  
Klara Brinzaniuc ◽  
Simona Gurzu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Histological Study ◽  
Collagen Scaffold ◽  
Bone Defects ◽  
Collagen Scaffolds ◽  
In Vivo Evaluation ◽  
Calvarial Bone ◽  
Bone Apposition

The use of collagen scaffolds and stem cells for obtaining a tissue-engineering complex has been an important concept in promoting repair and regeneration of the bone tissue. Such units represent important steps in the development of an ideal scaffold-cell complex that would sustain new bone apposition. The aim of our study was to perform a histologic evaluation of the healing of critical-sized bone defects, using a biologic collagen scaffold with adipose-derived mesenchymal stem cells, in comparison to negative controls created in the adjacent bone. We used 16 Wistar rats and according to the study design 2 calvarial bone defects were created in each animal, one was filled with collagen seeded with adipose-derived stem cells and the other one was considered negative control. During the following month, at weekly intervals, the animals were euthanized and the specimens from bone defects were histologically evaluated. The results showed that these scaffolds were highly biocompatible as only moderate inflammation no rejection reactions were observed. Furthermore, the first signs of osseous healing appeared after two weeks accompanied by angiogenesis. Collagen scaffolds seeded with adipose-derived mesenchymal stem cells can be considered a promising treatment option in bone regeneration of large defects.

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.

Role of Discoidin Domain Receptor 2 in Craniofacial Bone Regeneration

2021 ◽  
pp. 002203452110074
Author(s):  
A. Binrayes ◽  
C. Ge ◽  
F.F. Mohamed ◽  
R.T. Franceschi
Keyword(s):  
Bone Regeneration ◽  
Healing Process ◽  
Congenital Defects ◽  
Calvarial Bone ◽  
Discoidin Domain Receptor ◽  
Skeletal Defects ◽  
Discoidin Domain Receptor 2 ◽  
Collagen Receptor ◽  
Deficient Mice

Bone loss caused by trauma, neoplasia, congenital defects, or periodontal disease is a major cause of disability and human suffering. Skeletal progenitor cell–extracellular matrix interactions are critical for bone regeneration. Discoidin domain receptor 2 (DDR2), an understudied collagen receptor, plays an important role in skeletal development. Ddr2 loss-of-function mutations in humans and mice cause severe craniofacial and skeletal defects, including altered cranial shape, dwarfing, reduced trabecular and cortical bone, alveolar bone/periodontal defects, and altered dentition. However, the role of this collagen receptor in craniofacial regeneration has not been examined. To address this, calvarial subcritical-size defects were generated in wild-type (WT) and Ddr2-deficient mice. The complete bridging seen in WT controls at 4 wk postsurgery was not observed in Ddr2-deficient mice even after 12 wk. Quantitation of defect bone area by micro–computed tomography also revealed a 50% reduction in new bone volume in Ddr2-deficient mice. Ddr2 expression during calvarial bone regeneration was measured using Ddr2-LacZ knock-in mice. Expression was restricted to periosteal surfaces of uninjured calvarial bone and, after injury, was detected in select regions of the defect site by 3 d postsurgery and expanded during the healing process. The impaired bone healing associated with Ddr2 deficiency may be related to reduced osteoprogenitor or osteoblast cell proliferation and differentiation since knockdown/knockout of Ddr2 in a mesenchymal cell line and primary calvarial osteoblast cultures reduced osteoblast differentiation while Ddr2 overexpression was stimulatory. In conclusion, Ddr2 is required for cranial bone regeneration and may be a novel target for therapy.

scholarly journals Bmp Induces Osteoblast Differentiation through both Smad4 and mTORC1 Signaling

2016 ◽  
Vol 37 (4) ◽  
Author(s):  
Courtney M. Karner ◽  
Seung-Yon Lee ◽  
Fanxin Long
Keyword(s):  
Protein Synthesis ◽  
Intracellular Signaling ◽  
Osteoblast Differentiation ◽  
De Novo ◽  
Bmp Signaling ◽  
Endoplasmic Reticulum Stress Response ◽  
Versus Protein ◽  
Mtorc1 Signaling ◽  
General Protein Synthesis ◽  
General Protein

ABSTRACT The bone morphogenetic protein (Bmp) family of secreted molecules has been extensively studied in the context of osteoblast differentiation. However, the intracellular signaling cascades that mediate the osteoblastogenic function of Bmp have not been fully elucidated. By profiling mRNA expression in the bone marrow mesenchymal progenitor cell line ST2, we discover that BMP2 induces not only genes commonly associated with ossification and mineralization but also genes important for general protein synthesis. We define the two groups of genes as mineralization related versus protein anabolism signatures of osteoblasts. Although it induces the expression of several Wnt genes, BMP2 activates the osteogenic program largely independently of de novo Wnt secretion. Remarkably, although Smad4 is necessary for the activation of the mineralization-related genes, it is dispensable for BMP2 to induce the protein anabolism signature, which instead critically depends on the transcription factor Atf4. Upstream of Atf4, BMP2 activates mTORC1 to stimulate protein synthesis, resulting in an endoplasmic reticulum stress response mediated by Perk. Thus, Bmp signaling induces osteoblast differentiation through both Smad4- and mTORC1-dependent mechanisms.

scholarly journals Coactivation of Endogenous Wnt10b and Foxc2 by CRISPR Activation Enhances BMSC Osteogenesis and Promotes Calvarial Bone Regeneration

2020 ◽  
Vol 28 (2) ◽  
pp. 441-451 ◽  
Author(s):  
Mu-Nung Hsu ◽  
Kai-Lun Huang ◽  
Fu-Jen Yu ◽  
Po-Liang Lai ◽  
Anh Vu Truong ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Calvarial Bone ◽  
Crispr Activation

Ultraviolet-Crosslinkable and Injectable Chitosan/Hydroxyapatite Hybrid Hydrogel for Critical Size Calvarial Defect Repair In Vivo

2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Baoqiang Li ◽  
Lei Wang ◽  
Yu Hao ◽  
Daqing Wei ◽  
Ying Li ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Critical Size ◽  
Rabbit Model ◽  
Single Step ◽  
Calvarial Defect ◽  
Defect Model ◽  
Calvarial Bone ◽  
Hybrid Hydrogel ◽  
Defect Site

To promote bone regeneration in vivo using critical-size calvarial defect model, hybrid hydrogel was prepared by mixing chitosan with hydroxyapatite (HA) and ultraviolet (UV) irradiation in situ. The hydrosoluble, UV-crosslinkable and injectable N-methacryloyl chitosan (N-MAC) was synthesized via single-step N-acylation reaction. The chemical structure was confirmed by 1H-NMR and FTIR spectroscopy. N-MAC hydrogel presented a microporous structure with pore sizes ranging from 10 to 60 μm. Approximately 80% cell viability of N-MAC hydrogel against encapsulated 3T3 cell indicated that N-MAC is an emerging candidate for mimicking native extracellular matrix (ECM). N-MAC hydrogel hybridized with HA was used to accelerate regeneration of calvarial bone using rabbit model. The effects of hybrid hydrogels to promote bone regeneration were evaluated using critical size calvarial bone defect model. The healing effects of injectable hydrogels with/without HA for bone regeneration were investigated by analyzing X-ray image after 4 or 6 weeks. The results showed that the regenerated new bone for N-MAC 100 was significantly greater than N-MAC without HA and untreated controls. The higher HA content in N-MAC/HA hybrid hydrogel benefited the acceleration of bone regeneration. About 50% closure of defect site after 6 weeks postimplantation demonstrated potent osteoinductivity of N-MAC 100 UV-crosslinkable and injectable N-MAC/HA hybrid hydrogel would allow serving as a promising biomaterial for bone regeneration using the critical-size calvarial defect.

Guided Bone Regeneration in Calvarial Bone Defects Using Polytetrafluoroethylene Membranes

1995 ◽  
Vol 32 (4) ◽  
pp. 311-317 ◽  
Author(s):  
Carles Bosch ◽  
Birte Melsen ◽  
Karin Vargervik
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Dura Mater ◽  
Bone Defects ◽  
Guided Bone Regeneration ◽  
Parietal Bone ◽  
Bony Defect ◽  
Calvarial Bone ◽  
Double Membrane ◽  
Single Membrane

Guided bone regeneration is defined as controlled stimulation of new bone formation in a bony defect, either by osteogenesis, osteoinduction, or osteoconduction, re-establishing both structural and functional characteristics. Bony defects may be found as a result of congenital anomalies, trauma, neoplasms, or infectious conditions. Such conditions are often associated with severe functional and esthetic problems. Corrective treatment is often complicated by limitations in tissue adaptations. The aim of the investigation was to compare histologically the amount of bone formed in an experimentally created parietal bone defect protected with one or two polytetrafluoroethylene membranes with a contralateral control defect. A bony defect was created bilaterally in the parietal bone lateral to the sagittal suture in 29 6-month-old male Wistar rats. The animals were divided into two groups: (1) In the double membrane group (n=9), the left experimental bone defect was protected by an outer polytetrafluoroethylene membrane under the periosteum and parietal muscles and an inner membrane between the dura mater and the parietal bone. (2) In the single membrane group (n=20), only the outer membrane was placed. The right defect was not covered with any membrane and served as control. The animals were killed after 30 days. None of the control defects demonstrated complete or partial bone regeneration. In the single membrane group, the experimental site did not regenerate in 15 animals, partially in four, and completely in one. In the double membrane group, six of the experimental defects had complete closure with bone, two had partial closure, and one no closure. The use of two membranes protecting the bone edges of the parietal defect from the overlying tissues and underlying brain enhanced bone regeneration in experimental calvarial bone defects. The biologic role of the dura mater may not be of critical importance in new bone regeneration in these calvarial bone defects.

scholarly journals mTORC1 Signaling Promotes Osteoblast Differentiation from Preosteoblasts

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0130627 ◽  
Author(s):  
Jianquan Chen ◽  
Fanxin Long
Keyword(s):  
Osteoblast Differentiation ◽  
Mtorc1 Signaling
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