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Cells and Molecules in Bone Remodeling and Repair
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Cells and Molecules in Bone Remodeling and Repair

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 15731

Special Issue Editor

Prof. Dr. Jung Eun Kim

E-Mail Website
Guest Editor
Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
Interests: osteoblast/osteoclast differentiation; bone remodeling; bone development and homeostasis; bone metastasis; musculoskeletal diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Welcome to the Special Issue of Biochemistry Section of the International Journal of Molecular Sciences, on “Cells and Molecules in Bone Remodeling and Repair”.

Bone is a highly dynamic tissue that is continuously remodeled to replace old bone tissue with new bone tissue from birth throughout life. Bone is also repaired by complex and well-coordinated physiological processes during micro-crack or fracture healing. Thus, bone remodeling and repair are tightly regulated by the balance between bone cells and various factors in the bone microenvironment.

This Special Issue is focused on the cells and molecules that play a role in bone remodeling and repair. The molecular mechanisms of bone cells and molecules contributing to bone remodeling and repair provide a powerful platform for elucidating novel insights on bone pathophysiology. We very welcome the submission of original research articles and comprehensive reviews.

Prof. Dr. Jung Eun Kim
Guest Editor

Manuscript Submission Information

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Keywords

  • osteoblast
  • osteoclast
  • mesenchymal stem cell
  • hematopoietic stem cell
  • bone remodeling
  • bone repair
  • bone pathophysiology
  • bone microenvironment

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Published Papers (5 papers)

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Research

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15 pages, 3310 KiB  
Article
Photobiomodulation Dose–Response on Adipose-Derived Stem Cell Osteogenesis in 3D Cultures
by Daniella Da Silva, Anine Crous and Heidi Abrahamse
Int. J. Mol. Sci. 2024, 25(17), 9176; https://doi.org/10.3390/ijms25179176 - 23 Aug 2024
Viewed by 864
Abstract
Osteoporosis and other degenerative bone diseases pose significant challenges to global healthcare systems due to their prevalence and impact on quality of life. Current treatments often alleviate symptoms without fully restoring damaged bone tissue, highlighting the need for innovative approaches like stem cell [...] Read more.
Osteoporosis and other degenerative bone diseases pose significant challenges to global healthcare systems due to their prevalence and impact on quality of life. Current treatments often alleviate symptoms without fully restoring damaged bone tissue, highlighting the need for innovative approaches like stem cell therapy. Adipose-derived mesenchymal stem cells (ADMSCs) are particularly promising due to their accessibility, abundant supply, and strong differentiation potential. However, ADMSCs tend to favor adipogenic pathways, necessitating the use of differentiation inducers (DIs), three-dimensional (3D) hydrogel environments, and photobiomodulation (PBM) to achieve targeted osteogenic differentiation. This study investigated the combined effects of osteogenic DIs, a fast-dextran hydrogel matrix, and PBM at specific wavelengths and fluences on the proliferation and differentiation of immortalized ADMSCs into osteoblasts. Near-infrared (NIR) and green (G) light, as well as their combination, were used with fluences of 3 J/cm2, 5 J/cm2, and 7 J/cm2. The results showed statistically significant increases in alkaline phosphatase levels, a marker of osteogenic differentiation, with G light at 7 J/cm2 demonstrating the most substantial impact on ADMSC differentiation. Calcium deposits, visualized by Alizarin red S staining, appeared as early as 24 h post-treatment in PBM groups, suggesting accelerated osteogenic differentiation. ATP luminescence assays indicated increased proliferation in all experimental groups, particularly with NIR and NIR-G light at 3 J/cm2 and 5 J/cm2. MTT viability and LDH membrane permeability assays confirmed enhanced cell viability and stable cell health, respectively. In conclusion, PBM significantly influences the differentiation and proliferation of hydrogel-embedded immortalized ADMSCs into osteoblast-like cells, with G light at 7 J/cm2 being particularly effective. These findings support the combined use of 3D hydrogel matrices and PBM as a promising approach in regenerative medicine, potentially leading to innovative treatments for degenerative bone diseases. Full article
(This article belongs to the Special Issue Cells and Molecules in Bone Remodeling and Repair)
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15 pages, 2511 KiB  
Article
Engineering a Pro-Osteogenic Secretome through the Transient Silencing of the Gene Encoding Secreted Frizzled Related Protein 1
by Daniel García-Sánchez, Alberto González-González, Itzíar Álvarez-Iglesias, Mónica del Dujo-Gutiérrez, Alfonso Bolado-Carrancio, Matilde Certo, María Isabel Pérez-Núñez, José A. Riancho, José Carlos Rodríguez-Rey, Jesús Delgado-Calle and Flor María Pérez-Campo
Int. J. Mol. Sci. 2023, 24(15), 12399; https://doi.org/10.3390/ijms241512399 - 3 Aug 2023
Cited by 1 | Viewed by 1553
Abstract
The evidence sustaining the regenerative properties of mesenchymal stem cells’ (MSCs) secretome has prompted a paradigm change, where MSCs have shifted from being considered direct contributors to tissue regeneration toward being seen as cell factories for producing biotech medicines. We have previously designed [...] Read more.
The evidence sustaining the regenerative properties of mesenchymal stem cells’ (MSCs) secretome has prompted a paradigm change, where MSCs have shifted from being considered direct contributors to tissue regeneration toward being seen as cell factories for producing biotech medicines. We have previously designed a method to prime MSCs towards osteogenic differentiation by silencing the Wnt/β-Catenin inhibitor Sfpr1. This approach produces a significant increase in bone formation in osteoporotic mice. In this current work, we set to investigate the contribution of the secretome from the MSCs where Sfrp1 has been silenced, to the positive effect seen on bone regeneration in vivo. The conditioned media (CM) of the murine MSCs line C3H10T1/2, where Sfrp1 has been transiently silenced (CM-Sfrp1), was found to induce, in vitro, an increase in the osteogenic differentiation of this same cell line, as well as a decrease of the expression of the Wnt inhibitor Dkk1 in murine osteocytes ex vivo. A reduction in the RANKL/OPG ratio was also detected ex vivo, suggesting a negative effect of CM-Sfrp1 on osteoclastogenesis. Moreover, this CM significantly increases the mineralization of human primary MSCs isolated from osteoportotic patients in vitro. Proteomic analysis identified enrichment of proteins involved in osteogenesis within the soluble and vesicular fractions of this secretome. Altogether, we demonstrate the pro-osteogenic potential of the secretome of MSCs primmed in this fashion, suggesting that this is a valid approach to enhance the osteo-regenerative properties of MSCs’ secretome. Full article
(This article belongs to the Special Issue Cells and Molecules in Bone Remodeling and Repair)
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Review

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15 pages, 1261 KiB  
Review
Runx2 and Polycystins in Bone Mechanotransduction: Challenges for Therapeutic Opportunities
by Antonios N. Gargalionis, Christos Adamopoulos, Christos T. Vottis, Athanasios G. Papavassiliou and Efthimia K. Basdra
Int. J. Mol. Sci. 2024, 25(10), 5291; https://doi.org/10.3390/ijms25105291 - 13 May 2024
Cited by 3 | Viewed by 1176
Abstract
Bone mechanotransduction is a critical process during skeletal development in embryogenesis and organogenesis. At the same time, the type and level of mechanical loading regulates bone remodeling throughout the adult life. The aberrant mechanosensing of bone cells has been implicated in the development [...] Read more.
Bone mechanotransduction is a critical process during skeletal development in embryogenesis and organogenesis. At the same time, the type and level of mechanical loading regulates bone remodeling throughout the adult life. The aberrant mechanosensing of bone cells has been implicated in the development and progression of bone loss disorders, but also in the bone-specific aspect of other clinical entities, such as the tumorigenesis of solid organs. Novel treatment options have come into sight that exploit the mechanosensitivity of osteoblasts, osteocytes, and chondrocytes to achieve efficient bone regeneration. In this regard, runt-related transcription factor 2 (Runx2) has emerged as a chief skeletal-specific molecule of differentiation, which is prominent to induction by mechanical stimuli. Polycystins represent a family of mechanosensitive proteins that interact with Runx2 in mechano-induced signaling cascades and foster the regulation of alternative effectors of mechanotransuction. In the present narrative review, we employed a PubMed search to extract the literature concerning Runx2, polycystins, and their association from 2000 to March 2024. The keywords stated below were used for the article search. We discuss recent advances regarding the implication of Runx2 and polycystins in bone remodeling and regeneration and elaborate on the targeting strategies that may potentially be applied for the treatment of patients with bone loss diseases. Full article
(This article belongs to the Special Issue Cells and Molecules in Bone Remodeling and Repair)
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13 pages, 995 KiB  
Review
The Role of Low-Level Laser Therapy in Bone Healing: Systematic Review
by Micaela Berni, Alice Maria Brancato, Camilla Torriani, Valentina Bina, Salvatore Annunziata, Elena Cornella, Michelangelo Trucchi, Eugenio Jannelli, Mario Mosconi, Giulia Gastaldi, Laura Caliogna, Federico Alberto Grassi and Gianluigi Pasta
Int. J. Mol. Sci. 2023, 24(8), 7094; https://doi.org/10.3390/ijms24087094 - 12 Apr 2023
Cited by 22 | Viewed by 8070
Abstract
Low-level laser therapy (LLLT) is a treatment that is increasingly used in orthopedics practices. In vivo and in vitro studies have shown that low-level laser therapy (LLLT) promotes angiogenesis, fracture healing and osteogenic differentiation of stem cells. However, the underlying mechanisms during bone [...] Read more.
Low-level laser therapy (LLLT) is a treatment that is increasingly used in orthopedics practices. In vivo and in vitro studies have shown that low-level laser therapy (LLLT) promotes angiogenesis, fracture healing and osteogenic differentiation of stem cells. However, the underlying mechanisms during bone formation remain largely unknown. Factors such as wavelength, energy density, irradiation and frequency of LLLT can influence the cellular mechanisms. Moreover, the effects of LLLT are different according to cell types treated. This review aims to summarize the current knowledge of the molecular pathways activated by LLLT and its effects on the bone healing process. A better understanding of the cellular mechanisms activated by LLLT can improve its clinical application. Full article
(This article belongs to the Special Issue Cells and Molecules in Bone Remodeling and Repair)
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17 pages, 1684 KiB  
Review
The Cell-Specific Role of SHP2 in Regulating Bone Homeostasis and Regeneration Niches
by Jie Zhang, Chengxinyue Ye, Yufan Zhu, Jun Wang and Jin Liu
Int. J. Mol. Sci. 2023, 24(3), 2202; https://doi.org/10.3390/ijms24032202 - 22 Jan 2023
Cited by 3 | Viewed by 3148
Abstract
Src homology-2 containing protein tyrosine phosphatase (SHP2), encoded by PTPN11, has been proven to participate in bone-related diseases, such as Noonan syndrome (NS), metachondromatosis and osteoarthritis. However, the mechanisms of SHP2 in bone remodeling and homeostasis maintenance are complex and undemonstrated. The [...] Read more.
Src homology-2 containing protein tyrosine phosphatase (SHP2), encoded by PTPN11, has been proven to participate in bone-related diseases, such as Noonan syndrome (NS), metachondromatosis and osteoarthritis. However, the mechanisms of SHP2 in bone remodeling and homeostasis maintenance are complex and undemonstrated. The abnormal expression of SHP2 can influence the differentiation and maturation of osteoblasts, osteoclasts and chondrocytes. Meanwhile, SHP2 mutations can act on the immune system, vasculature and nervous system, which in turn affect bone development and remodeling. Signaling pathways regulated by SHP2, such as mitogen-activated protein kinase (MAPK), Indian hedgehog (IHH) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT), are also involved in the proliferation, differentiation and migration of bone functioning cells. This review summarizes the recent advances of SHP2 on osteogenesis-related cells and niche cells in the bone marrow microenvironment. The phenotypic features of SHP2 conditional knockout mice and underlying mechanisms are discussed. The prospective applications of the current agonists or inhibitors that target SHP2 in bone-related diseases are also described. Full clarification of the role of SHP2 in bone remodeling will shed new light on potential treatment for bone related diseases. Full article
(This article belongs to the Special Issue Cells and Molecules in Bone Remodeling and Repair)
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