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.

scholarly journals A Comprehensive Clinicopathologic Analysis Suggests that Vascular Endothelial Growth Factor (VEGF) is the Most Likely Mediator of Periosteal New Bone Formation (PNBF) Associated with Diverse Etiologies

2008 ◽  
Vol 1 ◽  
pp. CMAMD.S442
Author(s):  
Meredith A. Lakey ◽  
Michael J. Klein ◽  
Ona M. Faye-Petersen
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Bone Formation ◽  
Fracture Repair ◽  
Prostaglandin E ◽  
Hypertrophic Osteoarthropathy ◽  
Vascular Endothelial ◽  
New Bone Formation ◽  
Endothelial Growth Factor ◽  
Periosteal New Bone Formation

Periosteal new bone formation (PNBF) is the means by which appositional bone growth normally takes place on the surfaces of compact bone. Alterations in the periosteal microenvironment trigger complex interactions between osteoblasts and endothelial cells to promote PNBF. Physiologic processes like mechanical stress result in normal PNBF; but, a variety of pathologic processes result in excessive PNBF. The production of sufficient bone to be detectable by conventional radiography is a common feature of diverse etiologies, including infection; inflammation; prostaglandin E2 administration for ductal-dependent congenital heart disease; metabolic and hormonal abnormalities; neoplasms; fracture repair; systemic hypoxia; and hypertrophic osteoarthropathy. While the clinical settings and distribution of affected bone sites in these conditions are different, the histopathology of the PNBF is essentially identical; so, it seems logical that a common pathway might mediate them all. By combining the observations and insights gained from osseous research and studying the clinical pathology of these diverse conditions, we constructed a comprehensive pathway to explain PNBF. In doing so, it seems likely that Vascular Endothelial Growth Factor (VEGF) is the most likely common mediator of the pathways that lead to PNBF.

Strontium-Borosilicate-Co-Effects to Stimulate Bone Regeneration

2011 ◽  
Vol 685 ◽  
pp. 371-378
Author(s):  
Yu Hui Shen ◽  
Kui Bo Zhang ◽  
Hao Bo Pan ◽  
William W. Lu ◽  
Zhao Min Zheng ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Dissolution Rate ◽  
Bone Health ◽  
Bone Growth ◽  
Special Role ◽  
Psychomotor Skills ◽  
Rapid Degradation ◽  
Naturally Occurring ◽  
High Dissolution Rate

As a naturally-occurring trace element, boron involves many life processes including embryogenesis, bone growth and maintenance, immune function and psychomotor skills. Thus, the low chemical durable glass based on 3-fold coordination boron network former shows potential in delivering boron for bone health. However, its high dissolution rate may result in cytotoxicity. The addition of strontium seems to be an effective approach not only inhibits its rapid degradation, but delivers strontium as a ‘drug’ to enhance the ability of bone formation. Thus, strontium-incorporated borosilicate shows special role in bone regeneration, in particular in women past menopause.

Common Molecular Mechanisms Regulating Fetal Bone Formation and Adult Fracture Repair

2005 ◽  
pp. 45-55 ◽  
Author(s):  
Theodore Miclau ◽  
Richard A. Schneider ◽  
B. Frank Eames ◽  
Jill A. Helms
Keyword(s):  
Bone Formation ◽  
Molecular Mechanisms ◽  
Fracture Repair ◽  
Fetal Bone

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.

Successful Osteoinduction by Cell-Macroporous Biphasic HA-TCP Ceramic Matrix

2005 ◽  
Vol 288-289 ◽  
pp. 245-248 ◽  
Author(s):  
Hong In Shin ◽  
K.H. Kim ◽  
Inn Kyu Kang ◽  
Kyung Sik Oh
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Cellular Proliferation ◽  
Ceramic Matrix ◽  
Ectopic Bone Formation ◽  
Inflammatory Reactions ◽  
Cell Matrix ◽  
Cellular Attachment ◽  
Ectopic Bone

To improve the potential of osteogenic repair, we developed macroporous biphasic hydroxyapatite-tricalcium phosphate (HA-TCP) ceramic and evaluated its efficiency as a scaffold for tissue engineered bone regeneration, which allows for appropriate cellular attachment and proliferation with osteogenic differentiation by evaluating ectopic bone formation ability after the implantation of cell-matrix construct in the skid mice subcutaneous pouches for 3 weeks. The macroporous biphasic HA-TCP ceramic matrix, with an average porosity of 86% and 200 µm mean pore size, provided favorable conditions for the attachment of cultured bone marrow derived osteoblastic cells along its inner surfaces in a filed up pattern and the active proliferation of them. The implanted cell-matrix constructs in the subcutaneous pouches induced favorable ectopic bone formation without any remarkable inflammatory reactions. These findings suggest that the biphasic HA-TCP ceramic matrix with macroporous structure has excellent biocompatibility, and that it allows for favorable cellular attachment with the acceleration of cellular proliferation and osteogenic differentiation support as well. Thus, with the controlled biodegradability, the biphasic HA-TCP ceramic may be a promising scaffold for tissue engineered bone regeneration technology.

scholarly journals Role of CaMKK2 in Mechanically Induced Bone Formation

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Adam J. Warrick ◽  
Uma Sankar
Keyword(s):  
Protein Kinase ◽  
Bone Density ◽  
Bone Formation ◽  
Mechanical Stimulation ◽  
Internal Control ◽  
Molecular Mechanisms ◽  
Bone Growth ◽  
Lower Limbs ◽  
Alizarin Red ◽  
Bone Formation Rate

Background and Hypothesis: Mechanical stimulation of bone results in the translation of external forces into a cascade of structural and biochemical changes which work to increase bone density and decrease fracture healing time. The specific mechanisms contributing to these processes are areas of active investigation. Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a serine-threonine protein kinase with key roles in both the anabolic and catabolic pathways of bone remodeling. We hypothesize that the absence of CaMKK2 potentiates an increase in bone density as a response to mechanical stimulation. Experimental Design or Project Methods: The right ulna of anesthetized C57BL/6 mice were loaded for 220 cycles at 2 Hz and with peak forces specific to both sex and genotype. Loading was completed using an electro actuator (Bose ElectroForce 3200; EnduraTEC, Minnetonka, MN, USA) and was repeated on days 3, 5, 8 and 10 after the initial procedure. The non-loaded left ulna served as an internal control. Calcein and alizarin red were administered intraperitoneally on days 9 and 16 respectively. Mice were sacrificed on day 19 after the initial load; blood and long bones of the lower limbs were collected for analysis. Results: Bone volumetric analyses will be measured using microcomputed tomography, bone formation rate will be assessed using dynamic histomorphometry measurements of double fluorochrome labeling, and cellular and molecular mechanisms will be assessed using histology, immunohistochemistry and real-time reverse transcription-polymerase chain reaction. These data are currently forthcoming. Conclusion and Potential Impact: Clinical outcomes of conditions ranging from stress fractures to osteoporosis may be improved by an increased understanding of the mechanisms through which bone growth is augmented. Expanded knowledge of these pathways may provide opportunities for the development of novel therapies which decrease healing times in the event of injury and increase bone density to combat degenerative disease states.

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 TGF-β prevents the denervation-induced reduction of bone formation and promotes the bone regeneration through inhibiting ubiquitin-proteasome pathway

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Zhen Yu ◽  
Ye Li ◽  
Yining Wang ◽  
Yuting Chen ◽  
Mengfan Wu ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Transforming Growth Factor Beta ◽  
Bone Growth ◽  
Transforming Growth Factor ◽  
Multifunctional Protein ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Tgf Β1

Abstract Background: Transforming growth factor beta (TGF-β) can stimulate osteogenesis as a multifunctional protein. The present study was to explore if TGF-β can prevent denervation-induced reduction of bone formation. Materials & methods: The 6-week-old male mice were treated with recombinant human TGF-β1 (rhTGF-β1). Bone formation, endochondral bone growth rates, and gene expression of osteoblast markers were measured in the skeletal tissue by real-time PCR. Results: RhTGF-β1 treatment prevented the denervation-induced decrease in bone formation rates, endochondral growth, and expression of Cbfa1/Runx2 (runt-related transcription factor 2), Ostecalcin (OC), and ColIA1. TGF-β1 partially inhibited the denervation-induced ubiquitination of Cbfa1/Runx2 in mouse cancellous bones via ubiquitin-proteasome pathway. Conclusion: TGF-β prevents denervation-induced reduction of bone formation and promotes the bone regeneration through inhibiting ubiquitin-proteasome pathway at least partially.

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