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Applied Sciences
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Bone Histogenesis and Regeneration
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Bone Histogenesis and Regeneration

A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 19293

Special Issue Editors

Prof. Carla Palumbo

E-Mail Website
Guest Editor
Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, Largo del Pozzo 71, 41124 Modena, Italy
Interests: histophysiopathology of calcified tissues; bone cells; osteocyte; bone remodeling; bone alterations; bone regeneration
Dr. Alberto Smargiassi

E-Mail Website
Co-Guest Editor
Indiana Center for Musculoskeletal Health, IUPUI, Indianapolis, IN, USA
Interests: study of the bone-muscle crosstalk with a particular focus on the synergistic effect of contracting muscles metabolites and mechanical loading on bone; in-vitro and in-vivo study of the effects of mechanical stress on Osteocytes

Special Issue Information

Dear Colleagues,

The sophisticated processes leading to bone histogenesis (during skeletal organogenesis and bone turnover) and bone regeneration (after injuries or bone diseases) are currently not fully elucidated. It is not only bone cells that are involved in bone formation but also other tissues/organs (skeletal muscles, adipose tissue, etc.), acting in endocrine/paracrine-like manners via crosstalk between various actors belonging to different systems. Morphological changes as well as signaling pathways occurring during bone formation are to be deepened in a translational perspective. Collecting data from different fields (morphofunctional investigations, biomolecular analysis, clinical experimentations) is crucial to obtain interdisciplinary approaches with the final goal to improve tissue engineering strategies, in particular aimed at bone regeneration. This is particularly pivotal in a society with prolonged life expectancy, having the consequence to observe various pathologies, increasingly affecting the aging subjects. Focusing on the skeletal system, not only does bone fragility induce more susceptibility to fractures (often not accompanied by a good self-repairing ability), but metabolic imbalances also often induce failed bone regeneration. We hope that researchers with different expertises will consider contributing to this Special Issue, as it is only by sharing knowledge that we can hope to solve the problem of bone regeneration in critical conditions.

Prof. Carla Palumbo
Dr. Alberto Smargiassi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Applied Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bone regeneration
  • bone histophysiopathology
  • bone diseases and related pathologies
  • bone–muscle crosstalk
  • signaling pathways
  • bone tissue engineering

Published Papers (6 papers)

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Research

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9 pages, 2888 KiB  
Article
Effect of the Tumor Suppressor miR-320a on Viability and Functionality of Human Osteosarcoma Cell Lines Compared to Primary Osteoblasts
by Laura De-Ugarte, Susanna Balcells, Robert Guerri-Fernandez, Daniel Grinberg, Adolfo Diez-Perez, Xavier Nogues and Natalia Garcia-Giralt
Appl. Sci. 2020, 10(8), 2852; https://doi.org/10.3390/app10082852 - 20 Apr 2020
Cited by 1 | Viewed by 1512
Abstract
The miR-320a regulates a number of genes involved in various physiological processes. In particular, it has been reported as a tumor suppressor in several types of human cancers and involved in osteoporotic fracture and osteoblast function. Hence, the role of miR-320a has been [...] Read more.
The miR-320a regulates a number of genes involved in various physiological processes. In particular, it has been reported as a tumor suppressor in several types of human cancers and involved in osteoporotic fracture and osteoblast function. Hence, the role of miR-320a has been evaluated in tumor cells and in primary cells in a separated context, but its effect has never been explored in a comparative manner. The present study aims to evaluate the cellular effects of miR-320a on human osteosarcoma cell lines (MG-63 and U2OS) compared to that on primary human osteoblasts (hOBs). miR-320a was either overexpressed or inhibited in all cell lines, and cell proliferation and viability were analyzed. Additionally, the effects of miR-320a on matrix mineralization, alkaline phosphatase activity, and oxidative stress were also evaluated in order to assess osteoblast functionality. In osteosarcoma cells, miR-320a overexpression reduced cell viability and proliferation, while in hOB cell viability was not affected and proliferation even was increased. The overexpression of miR-320a in both osteosarcoma cells and hOBs reduced the mineralization capacity. Finally, an increased oxidative stress was detected in all cells after miR-320a overexpression mainly in osteosarcoma. In conclusion, the overexpression of miR-320a increased stress oxidation levels, which could be involved in the reduced osteoblast performance, even though the cell viability was only affected in osteosarcoma cells. Full article
(This article belongs to the Special Issue Bone Histogenesis and Regeneration)
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Review

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16 pages, 795 KiB  
Review
The Role of Proteasome Inhibitors in Multiple Myeloma Bone Disease and Bone Metastasis: Effects on Osteoblasts and Osteocytes
by Denise Toscani, Luisa Craviotto and Nicola Giuliani
Appl. Sci. 2021, 11(10), 4642; https://doi.org/10.3390/app11104642 - 19 May 2021
Cited by 3 | Viewed by 1847
Abstract
The alterations of bone remodeling are typical of multiple myeloma (MM) patients where the uncoupled and unbalanced bone remodeling caused the onset of osteolytic lesions. Moreover, bone metastasis occurs in the majority of patients with breast and prostate cancer. Skeletal-related events negatively impact [...] Read more.
The alterations of bone remodeling are typical of multiple myeloma (MM) patients where the uncoupled and unbalanced bone remodeling caused the onset of osteolytic lesions. Moreover, bone metastasis occurs in the majority of patients with breast and prostate cancer. Skeletal-related events negatively impact on quality of life by increasing the vulnerability to fractures. Several bone-targeting treatments have been developed to control bone pain and pathological fractures, including bisphosphonates and Denosumab. Nevertheless, these agents act by inhibiting osteoclast activity but do not improve bone formation. Proteasome inhibitors (PIs) have shown bone anabolic effects and encouraging results in stimulating osteoblast differentiation and bone healing. Among these, the first-in-class bortezomib and the second-generation PIs, carfilzomib, and ixazomib regulate the bone remodeling process by controlling the degradation of several bone proteins. PIs have been recently proven to also be efficacious in blocking MM-induced osteocyte death providing new possible therapeutic use in the management of bone loss. PIs have significant side effects that limit their use as bone anabolic strategy. Multiple alternative approaches have been made. The conjugation of PIs with bisphosphonates, which can target them to bone, showed good results in terms of bone anabolic activity. However, the clinical implications of these effects require further investigations. Full article
(This article belongs to the Special Issue Bone Histogenesis and Regeneration)
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15 pages, 1127 KiB  
Review
Estrogen Signaling in Bone
by Nuria Lara-Castillo
Appl. Sci. 2021, 11(10), 4439; https://doi.org/10.3390/app11104439 - 13 May 2021
Cited by 10 | Viewed by 5780
Abstract
Estrogen plays important roles in bone homeostasis throughout a person’s life, including longitudinal bone growth, bone healing, and adaptation to mechanical forces. Estrogen exerts its action by binding to its multiple receptors in the cell membrane and cytoplasm. Until now at least three [...] Read more.
Estrogen plays important roles in bone homeostasis throughout a person’s life, including longitudinal bone growth, bone healing, and adaptation to mechanical forces. Estrogen exerts its action by binding to its multiple receptors in the cell membrane and cytoplasm. Until now at least three estrogen receptors (ER) have been reported: ER alpha (ERα), ER beta (ERβ), and G-protein coupled estrogen receptor 1 (GPER1) also known as GP30. Recently it has been observed that estrogen crosstalk with other signaling pathways helping to understand its wide effects in bone homeostasis. Abrupt loss of estrogen production experienced by menopausal women is associated with the rapid loss of bone mass ultimately leading to osteoporosis. The detrimental results during its absence with aging and the increased life expectancy of current and future generations make it of high importance to fully understand its mechanism of action. This review article aims to update on (1) the molecular mechanism of action of estrogen in the skeletal system, (2) ERs expression in different bone cells, (3) recent reported ER mutations resulting in pathological human conditions, and (4) role of estrogen signaling during bone healing. Full article
(This article belongs to the Special Issue Bone Histogenesis and Regeneration)
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16 pages, 8088 KiB  
Review
Static Osteogenesis versus Dynamic Osteogenesis: A Comparison between Two Different Types of Bone Formation
by Marzia Ferretti and Carla Palumbo
Appl. Sci. 2021, 11(5), 2025; https://doi.org/10.3390/app11052025 - 25 Feb 2021
Cited by 9 | Viewed by 2614
Abstract
In contrary to what has traditionally been believed, bone formation can occur through two different types of osteogenesis: static (SO) and dynamic (DO) osteogenesis, which are thus named because the former is characterized by pluristratified cords of unexpectedly stationary osteoblasts which differentiate at [...] Read more.
In contrary to what has traditionally been believed, bone formation can occur through two different types of osteogenesis: static (SO) and dynamic (DO) osteogenesis, which are thus named because the former is characterized by pluristratified cords of unexpectedly stationary osteoblasts which differentiate at a fairly constant distance from the blood capillaries and transform into osteocytes without moving from the onset site, while the latter is distinguished by the well-known typical monostratified laminae of movable osteoblasts. The two types of osteogenesis differ in multiple aspects from both structural and functional viewpoints. Besides osteoblast arrangement, polarization, and motion, SO and DO differ in terms of time of occurrence (first SO and later DO), conditioning factors to which they are sensitive (endothelial-derived cytokines or mechanical loading, respectively), distribution of osteocytes to which they give rise (haphazard or ordered in planes, respectively), the collagen texture resulting from the different deposition types (woven or lamellar, respectively), the mechanical properties of the bone they form (poor for SO due to the high cellularity and woven texture and good for DO since osteocytes are located in more suitable conditions to perceive loading), and finally the functions of each, i.e., SO provides a preliminary rigid scaffold on which DO can take place, while DO produces bone tissue according to mechanical/metabolic needs. Full article
(This article belongs to the Special Issue Bone Histogenesis and Regeneration)
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12 pages, 863 KiB  
Review
The Role of Bone Stem Cell Niches in Bone Metastasis
by Roberto Tamma, Tiziana Annese and Domenico Ribatti
Appl. Sci. 2020, 10(21), 7713; https://doi.org/10.3390/app10217713 - 31 Oct 2020
Viewed by 2008
Abstract
In post-natal life, stem cells contribute to the preservation of many tissues. In adults, stem cells remain localized, in particular, specialized microanatomical areas named as niches, which are crucial in the control of stem cell quiescence and activity through the production of many [...] Read more.
In post-natal life, stem cells contribute to the preservation of many tissues. In adults, stem cells remain localized, in particular, specialized microanatomical areas named as niches, which are crucial in the control of stem cell quiescence and activity through the production of many regulatory signals. Bone physiologically includes both the endosteal niche and the vascular niche, which are involved in the attraction, retention and release of the residing stem cells during the formation of new vessels as well as in the control of the differentiation of bone-forming osteoblasts and bone-resorbing osteoclasts. In tumors, cancer cells are able to take control of the niches to support all the stages of the tumorigenesis, transforming them in the so-called pre-metastatic and metastatic niches. Hence, there is emerging importance of the interactions between cancer cells, bone cells and niches in driving metastatic progression. This review article summarizes the literature data concerning the role of bone vascular and endosteal niches in the regulation of bone metastasis, focusing on their cellular and molecular interactions and the potential therapeutic approaches. Full article
(This article belongs to the Special Issue Bone Histogenesis and Regeneration)
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28 pages, 4409 KiB  
Review
Bone Healing Evaluation Following Different Osteotomic Techniques in Animal Models: A Suitable Method for Clinical Insights
by Alexandre Anesi, Mattia Di Bartolomeo, Arrigo Pellacani, Marzia Ferretti, Francesco Cavani, Roberta Salvatori, Riccardo Nocini, Carla Palumbo and Luigi Chiarini
Appl. Sci. 2020, 10(20), 7165; https://doi.org/10.3390/app10207165 - 14 Oct 2020
Cited by 19 | Viewed by 4846
Abstract
Osteotomy is a common step in oncological, reconstructive, and trauma surgery. Drilling and elevated temperature during osteotomy produce thermal osteonecrosis. Heat and associated mechanical damage during osteotomy can impair bone healing, with consequent failure of fracture fixation or dental implants. Several ex vivo [...] Read more.
Osteotomy is a common step in oncological, reconstructive, and trauma surgery. Drilling and elevated temperature during osteotomy produce thermal osteonecrosis. Heat and associated mechanical damage during osteotomy can impair bone healing, with consequent failure of fracture fixation or dental implants. Several ex vivo studies on animal bone were recently focused on heating production during osteotomy with conventional drill and piezoelectric devices, particularly in endosseous dental implant sites. The current literature on bone drilling and osteotomic surface analysis is here reviewed and the dynamics of bone healing after osteotomy with traditional and piezoelectric devices are discussed. Moreover, the methodologies involved in the experimental osteotomy and clinical studies are compared, focusing on ex vivo and in vivo findings. Full article
(This article belongs to the Special Issue Bone Histogenesis and Regeneration)
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