scholarly journals Effects of Extracellular Osteoanabolic Agents on the Endogenous Response of Osteoblastic Cells

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2383
Author(s):  
Giulia Alloisio ◽  
Chiara Ciaccio ◽  
Giovanni Francesco Fasciglione ◽  
Umberto Tarantino ◽  
Stefano Marini ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Cells ◽  
Fracture Repair ◽  
Osteoblastic Cells ◽  
Mineral Apposition Rate ◽  
Genetic Determinants ◽  
Cellular Processes ◽  
Continuous Response ◽  
Extracellular Stimuli

The complex multidimensional skeletal organization can adapt its structure in accordance with external contexts, demonstrating excellent self-renewal capacity. Thus, optimal extracellular environmental properties are critical for bone regeneration and inextricably linked to the mechanical and biological states of bone. It is interesting to note that the microstructure of bone depends not only on genetic determinants (which control the bone remodeling loop through autocrine and paracrine signals) but also, more importantly, on the continuous response of cells to external mechanical cues. In particular, bone cells sense mechanical signals such as shear, tensile, loading and vibration, and once activated, they react by regulating bone anabolism. Although several specific surrounding conditions needed for osteoblast cells to specifically augment bone formation have been empirically discovered, most of the underlying biomechanical cellular processes underneath remain largely unknown. Nevertheless, exogenous stimuli of endogenous osteogenesis can be applied to promote the mineral apposition rate, bone formation, bone mass and bone strength, as well as expediting fracture repair and bone regeneration. The following review summarizes the latest studies related to the proliferation and differentiation of osteoblastic cells, enhanced by mechanical forces or supplemental signaling factors (such as trace metals, nutraceuticals, vitamins and exosomes), providing a thorough overview of the exogenous osteogenic agents which can be exploited to modulate and influence the mechanically induced anabolism of bone. Furthermore, this review aims to discuss the emerging role of extracellular stimuli in skeletal metabolism as well as their potential roles and provide new perspectives for the treatment of bone disorders.

scholarly journals Matrix Vesicles: Role in Bone Mineralization and Potential Use as Therapeutics

2021 ◽  
Vol 14 (4) ◽  
pp. 289
Author(s):  
Sana Ansari ◽  
Bregje W. M. de de Wildt ◽  
Michelle A. M. Vis ◽  
Carolina E. de de Korte ◽  
Keita Ito ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Cells ◽  
Bone Mineralization ◽  
Recipient Cell ◽  
Organic Matrix ◽  
Matrix Vesicles ◽  
Matrix Mineralization

Bone is a complex organ maintained by three main cell types: osteoblasts, osteoclasts, and osteocytes. During bone formation, osteoblasts deposit a mineralized organic matrix. Evidence shows that bone cells release extracellular vesicles (EVs): nano-sized bilayer vesicles, which are involved in intercellular communication by delivering their cargoes through protein–ligand interactions or fusion to the plasma membrane of the recipient cell. Osteoblasts shed a subset of EVs known as matrix vesicles (MtVs), which contain phosphatases, calcium, and inorganic phosphate. These vesicles are believed to have a major role in matrix mineralization, and they feature bone-targeting and osteo-inductive properties. Understanding their contribution in bone formation and mineralization could help to target bone pathologies or bone regeneration using novel approaches such as stimulating MtV secretion in vivo, or the administration of in vitro or biomimetically produced MtVs. This review attempts to discuss the role of MtVs in biomineralization and their potential application for bone pathologies and bone regeneration.

Interactive effects of PTH and mechanical stress on nitric oxide and PGE2 production by primary mouse osteoblastic cells

2003 ◽  
Vol 285 (3) ◽  
pp. E608-E613 ◽  
Author(s):  
Astrid D. Bakker ◽  
Manon Joldersma ◽  
Jenneke Klein-Nulend ◽  
Elisabeth H. Burger
Keyword(s):  
Nitric Oxide ◽  
Fluid Flow ◽  
Bone Formation ◽  
Mechanical Stress ◽  
Bone Cells ◽  
Osteoblastic Cells ◽  
Prostaglandin E ◽  
No Production ◽  
Simultaneous Application ◽  
Primary Mouse

Parathyroid hormone (PTH) and mechanical stress both stimulate bone formation but have opposite effects on bone resorption. PTH increased loading-induced bone formation in a rat model, suggesting that there is an interaction of these stimuli, possibly at the cellular level. To investigate whether PTH can modulate mechanotransduction by bone cells, we examined the effect of 10-9 M human PTH-(1-34) on fluid flow-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production by primary mouse osteoblastic cells in vitro. Mechanical stress applied by means of a pulsating fluid flow (PFF; 0.6 ± 0.3 Pa at 5 Hz) stimulated both NO and PGE2 production twofold. In the absence of stress, PTH also caused a twofold increase in PGE2 production, but NO release was not affected and remained low. Simultaneous application of PFF and PTH nullified the stimulating effect of PFF on NO production, whereas PGE2 production was again stimulated only twofold. Treatment with PTH alone reduced NO synthase (NOS) enzyme activity to undetectable levels. We speculate that PTH prevents stress-induced NO production via the inhibition of NOS, which will also inhibit the NO-mediated upregulation of PGE2 by stress, leaving only the NO-independent PGE2 upregulation by PTH. These results suggest that mechanical loading and PTH interact at the level of mechanotransduction.

Influence of Emdogain® Treatment onto K2O Incorporated Calcium Metaphosphate on Osteogenic Activation

2005 ◽  
Vol 284-286 ◽  
pp. 631-634
Author(s):  
Suk Young Kim ◽  
Chang Kuk You ◽  
Jae Ho Jeong ◽  
Eui Kyun Park ◽  
Shin Yoon Kim ◽  
...  
Keyword(s):  
Bone Formation ◽  
Physical Properties ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Ectopic Bone Formation ◽  
Bone Tissue Regeneration ◽  
Osteoblastic Cells ◽  
Average Pore ◽  
Ectopic Bone ◽  
Cell Scaffold

As a part of the efforts to develop a suitable scaffold optimizing bone regeneration that has similar physical properties to bone, we modified calcium metaphosphate (CMP) ceramics with K2O and evaluated their efficiency as a scaffold for tissue engineered bone tissue regeneration. Macroporous CMP ceramics modified by incorporation of 5% K2O to improve biodegradability were prepared to have 250 and 450 µm average pore sizes, respectively. The modified CMP ceramics were cultured with mouse primary calvarial osteoblastic cells in osteogenic media for 2 weeks and these cell-CMP ceramic constructs with or without Emdogain treatment were implanted in the SCID mice subcutaneous pouches. After 1, 2, and 3 weeks, the degree of ectopic bone formation was evaluated. The modified macroporous CMP ceramic-cell constructs treated with Emdogain induced ectopic bone formation, whereas the modified CMP ceramic-cell constructs without Emdogain treatment induced no ectopic bone formation. This result suggests that the Emdogain treatment on cell-scaffold constructs for tissue engineered bone regeneration may be effective for osteogenic activation of attached cells.

scholarly journals MicroRNAs at the Interface between Osteogenesis and Angiogenesis as Targets for Bone Regeneration

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 121 ◽  
Author(s):  
Leopold Fröhlich
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Molecular Mechanisms ◽  
Bone Growth ◽  
Active Role ◽  
Fracture Repair ◽  
Ectopic Bone ◽  
Complex Process ◽  
Great Relevance ◽  
Endothelial Growth Factor

Bone formation and regeneration is a multistep complex process crucially determined by the formation of blood vessels in the growth plate region. This is preceded by the expression of growth factors, notably the vascular endothelial growth factor (VEGF), secreted by osteogenic cells, as well as the corresponding response of endothelial cells, although the exact mechanisms remain to be clarified. Thereby, coordinated coupling between osteogenesis and angiogenesis is initiated and sustained. The precise interplay of these two fundamental processes is crucial during times of rapid bone growth or fracture repair in adults. Deviations in this balance might lead to pathologic conditions such as osteoarthritis and ectopic bone formation. Besides VEGF, the recently discovered important regulatory and modifying functions of microRNAs also support this key mechanism. These comprise two principal categories of microRNAs that were identified with specific functions in bone formation (osteomiRs) and/or angiogenesis (angiomiRs). However, as hypoxia is a major driving force behind bone angiogenesis, a third group involved in this process is represented by hypoxia-inducible microRNAs (hypoxamiRs). This review was focused on the identification of microRNAs that were found to have an active role in osteogenesis as well as angiogenesis to date that were termed “CouplingmiRs (CPLGmiRs)”. Outlined representatives therefore represent microRNAs that already have been associated with an active role in osteogenic-angiogenic coupling or are presumed to have its potential. Elucidation of the molecular mechanisms governing bone angiogenesis are of great relevance for improving therapeutic options in bone regeneration, tissue-engineering, and the treatment of bone-related diseases.

Skeletal unloading in rat decreases proliferation of rat bone and marrow-derived osteoblastic cells

1993 ◽  
Vol 264 (5) ◽  
pp. E790-E799 ◽  
Author(s):  
M. Machwate ◽  
E. Zerath ◽  
X. Holy ◽  
M. Hott ◽  
D. Modrowski ◽  
...  
Keyword(s):  
Bone Formation ◽  
Stromal Cells ◽  
Bone Cells ◽  
Marrow Stromal Cells ◽  
Osteoblastic Cells ◽  
Type Iii Collagen ◽  
Type I ◽  
Bone Surface ◽  
Skeletal Unloading ◽  
In Vitro Proliferation

The effects of skeletal unloading on osteoblastic cells were evaluated in tail-suspended rats. Hindlimb elevation for 14 days induced osteopenia, decreased histomorphometric indexes of bone formation in tibial metaphysis, and reduced plasma osteocalcin and alkaline phosphatase (ALP) levels compared with controls. The in vitro proliferation of osteoblastic cells isolated from the endosteal bone surface of suspended tibias was decreased by 42 and 31% at 2 and 4 days of culture, respectively, compared with controls, as shown by [3H]thymidine labeling and cell number. The proliferation of ALP-positive marrow stromal cells was also decreased by 20–24% at 1 and 2 days of culture. However, ALP activity in bone-derived cells and marrow stromal cells was not different in unloaded and control rats, and the number of bone cells synthesizing osteocalcin, osteonectin, and type I or type III collagen was identical in the two groups. The results indicate that the inhibition of bone formation induced by skeletal unloading is related to a decreased proliferation of putative osteoblast precursor cells present along the endosteal bone surface and in the marrow stroma.

scholarly journals Phosphate graphene as an intrinsically osteoinductive scaffold for stem cell-driven bone regeneration

2019 ◽  
Vol 116 (11) ◽  
pp. 4855-4860 ◽  
Author(s):  
Anne M. Arnold ◽  
Brian D. Holt ◽  
Leila Daneshmandi ◽  
Cato T. Laurencin ◽  
Stefanie A. Sydlik
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Cells ◽  
Standard Of Care ◽  
Ectopic Bone Formation ◽  
Bone Morphogenetic Protein 2 ◽  
Ectopic Bone ◽  
Human Bone Morphogenetic Protein

Synthetic, resorbable scaffolds for bone regeneration have potential to transform the clinical standard of care. Here, we demonstrate that functional graphenic materials (FGMs) could serve as an osteoinductive scaffold: recruiting native cells to the site of injury and promoting differentiation into bone cells. By invoking a Lewis acid-catalyzed Arbuzov reaction, we are able to functionalize graphene oxide (GO) to produce phosphate graphenes (PGs) with unprecedented control of functional group density, mechanical properties, and counterion identity. In aqueous environments, PGs release inducerons, including Ca2+ and PO43−. Calcium phosphate graphene (CaPG) intrinsically induces osteogenesis in vitro and in the presence of bone marrow stromal cells (BMSCs), can induce ectopic bone formation in vivo. Additionally, an FGM can be made by noncovalently loading GO with the growth factor recombinant human bone morphogenetic protein 2 (rhBMP-2), producing a scaffold that induces ectopic bone formation with or without BMSCs. The FGMs reported here are intrinsically inductive scaffolds with significant potential to revolutionize the regeneration of bone.

scholarly journals Bone-Forming Peptide-4 Induces Osteogenic Differentiation and VEGF Expression on Multipotent Bone Marrow Stromal Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Mi Eun Kim ◽  
Jong Keun Seon ◽  
Ju Yeon Kang ◽  
Taek Rim Yoon ◽  
Jun Sik Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Bone Repair ◽  
Fracture Repair ◽  
Marrow Stromal Cells ◽  
Dependent Manner

Bone morphogenetic proteins (BMPs) have been widely used as treatment for bone repair. However, clinical trials on fracture repair have challenged the effectiveness of BMPs and suggested that delivery of multipotent bone marrow stromal cells (BMSCs) might be beneficial. During bone remodeling and bone fracture repair, multipotent BMSCs differentiate into osteoblasts or chondrocytes to stimulate bone formation and regeneration. Stem cell-based therapies provide a promising approach for bone formation. Extensive research has attempted to develop adjuvants as specific stimulators of bone formation for therapeutic use in patients with bone resorption. We previously reported for the first time bone-forming peptides (BFPs) that induce osteogenesis and bone formation. BFPs are also a promising osteogenic factor for prompting bone regeneration and formation. Thus, the aim of the present study was to investigate the underlying mechanism of a new BFP-4 (FFKATEVHFRSIRST) in osteogenic differentiation and bone formation. This study reports that BFP-4 induces stronger osteogenic differentiation of BMSCs than BMP-7. BFP-4 also induces ALP activity, calcium concentration, and osteogenic factors (Runx2 and osteocalcin) in a dose dependent manner in BMSCs. Therefore, these results indicate that BFP-4 can induce osteogenic differentiation and bone formation. Thus, treatment of multipotent BMSCs with BFP-4 enhanced osteoblastic differentiation and displayed greater bone-forming ability than BMP-7 treatment. These results suggest that BFP-4-stimulated cell therapy may be an efficient and cost-effective complement to BMP-7-based clinical therapy for bone regeneration and formation.

scholarly journals Stimulation of Fos- and Jun-related Genes During Distraction Osteogenesis

2003 ◽  
Vol 51 (9) ◽  
pp. 1161-1168 ◽  
Author(s):  
Dina Lewinson ◽  
Adi Rachmiel ◽  
Souhir Rihani-Bisharat ◽  
Zaki Kraiem ◽  
Pesia Schenzer ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Mechanical Stimulation ◽  
Bone Cells ◽  
Bone Development ◽  
Early Response ◽  
Northern Blotting ◽  
Fracture Repair ◽  
Regeneration System ◽  
Repair Tissue

Bone cells respond to mechanical stimulation by gene expression. The molecular events involved in the translation of mechanical stimulation into cell proliferation and bone formation are not yet well understood. We looked for the expression of early-response genes of the AP-1 transcription factor complex in an in vivo bone regeneration system subjected to mechanical forces because these genes were found to be related to mechanotransduction and important for bone development. Sheep maxillary bone was distracted daily for 15 days. c-Jun and c-Fos were evaluated by Northern blotting analysis and immunohistochemistry in biopsy specimens removed at 8 and 15 days and were compared with post-osteotomy but not distracted repair tissue. Elevated levels of c-Jun and c-Fos mRNA were found after 8 days of distraction. Likewise, mesenchyme-like and fibroblast-like cells composing the 8-day distracted regeneration tissue showed increases in the intensity of immunostaining compared to cells in the corresponding non-distracted fracture repair tissue. After 15 days of distraction, when bone trabeculae start to form distally and proximally in the distracted regeneration tissue, mostly preosteoblasts and osteoblasts retained c-Fos and c-Jun immunoreactivity, similar to bone-associated cells in control non-distracted fracture repair tissue. We propose that the elevated expression of c-Jun and c-Fos is related to mechanical stimulation in this in vivo bone regeneration system.

Dietary Calcium Supplementation Suppresses Bone Formation in Magnesium-Deficient Rats

2006 ◽  
Vol 76 (3) ◽  
pp. 111-116 ◽  
Author(s):  
Hiroshi Matsuzaki ◽  
Misao Miwa
Keyword(s):  
Bone Formation ◽  
Calcium Supplementation ◽  
Control Diet ◽  
Formation Rate ◽  
Dietary Calcium ◽  
Mineral Apposition Rate ◽  
Control Group ◽  
Deficient Diet ◽  
Bone Formation Rate ◽  
Male Wistar Rats

The purpose of this study was to clarify the effects of dietary calcium (Ca) supplementation on bone metabolism of magnesium (Mg)-deficient rats. Male Wistar rats were randomized by weight into three groups, and fed a control diet (control group), a Mg-deficient diet (Mg- group) or a Mg-deficient diet having twice the control Ca concentrations (Mg-2Ca group) for 14 days. Trabecular bone volume was significantly lower in the Mg - and Mg-2Ca groups than in the control group. Trabecular number was also significantly lower in the Mg - and Mg-2Ca groups than in the control group. Mineralizing bone surface, mineral apposition rate (MAR), and surface referent bone formation rate (BFR/BS) were significantly lower in the Mg - and Mg-2Ca groups than in the control group. Furthermore, MAR and BFR/BS were significantly lower in the Mg-2Ca group than in the Mg - group. These results suggest that dietary Ca supplementation suppresses bone formation in Mg-deficient rats.

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