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Molecular Mechanisms of Bone Healing
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Molecular Mechanisms of Bone Healing

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: closed (31 January 2022) | Viewed by 17058

Special Issue Editor

Prof. Dr. Emerito Carlos Rodriguez-Merchan

E-Mail Website
Guest Editor
1. Department of Orthopedic Surgery, La Paz University Hospital, 28046 Madrid, Spain
2. Osteoarticular Surgery Research, Institute for Health Research, La Paz University Hospital, Autonomous University of Madrid, 28046 Madrid, Spain
Interests: bone; tendon; ligament; muscle; hemophilia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is estimated that between 5% and 10% of bone fractures do not heal properly. Furthermore, there are currently no pharmacological treatments that help bone consolidation effectively. For this reason, better knowledge of the molecular mechanisms underlying bone healing is fundamental for the development of new treatments to accelerate it.

Bone tissue engineering (BTE) appears to be promising, although its success often depends on a “smart” scaffold that hosts and guides bone formation through the precursors of bone cells. Bone homeostasis basically depends on osteoblasts and osteoclasts in a continuous cycle of bone resorption and formation.

Studies on periosteum are essential, as it plays a crucial role in bone development and in the process of fracture healing. The role of macrophages as central regulators during all phases of bone repair must also be further investigated.

Research into the relationship between osteogenesis and angiogenesis is essential, as they are intimately linked during bone growth and regeneration in bone modeling and during bone homeostasis in bone remodeling.

The role of the leptin as an enhancer of osteogenesis induced by bone morphogenetic protein-9 (BMP9) should be further explored through cross-regulating BMP9 signaling through the JAK/STAT signaling pathway in mesenchymal stem cells (MSCs). Finally, the role of Morin, which could be beneficial in the regeneration of bone defects, should also be further studied.

Prof. Dr. Emerito Carlos Rodriguez-Merchan
Guest Editor

Manuscript Submission Information

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Keywords

  • bone
  • fracture
  • healing
  • bone tissue engineering
  • osteoblasts
  • osteoclasts, periosteum
  • osteogenesis
  • angiogenesis

Published Papers (5 papers)

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Research

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17 pages, 4349 KiB  
Article
The Role of PEMFs on Bone Healing: An In Vitro Study
by Laura Caliogna, Valentina Bina, Alice Maria Brancato, Giulia Gastaldi, Salvatore Annunziata, Mario Mosconi, Federico Alberto Grassi, Francesco Benazzo and Gianluigi Pasta
Int. J. Mol. Sci. 2022, 23(22), 14298; https://doi.org/10.3390/ijms232214298 - 18 Nov 2022
Cited by 3 | Viewed by 1707
Abstract
Bone responses to pulsed electromagnetic fields (PEMFs) have been extensively studied by using devices that expose bone cells to PEMFs to stimulate extracellular matrix (ECM) synthesis for bone and cartilage repair. The aim of this work was to highlight in which bone healing [...] Read more.
Bone responses to pulsed electromagnetic fields (PEMFs) have been extensively studied by using devices that expose bone cells to PEMFs to stimulate extracellular matrix (ECM) synthesis for bone and cartilage repair. The aim of this work was to highlight in which bone healing phase PEMFs exert their action. Specifically, we evaluated the effects of PEMFs both on human adipose mesenchymal stem cells (hASCs) and on primary human osteoblasts (hOBs) by testing gene and protein expression of early bone markers (on hASCs) and the synthesis of late bone-specific proteins (on hOBs) as markers of bone remodeling. Our results indicate that PEMFs seem to exert their action on bone formation, acting on osteogenic precursors (hASCs) and inducing the commitment towards the differentiation pathways, unlike mature and terminally differentiated cells (hOBs), which are known to resist homeostasis perturbation more and seem to be much less responsive than mesenchymal stem cells. Understanding the role of PEMFs on bone regenerative processes provides important details for their clinical application. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Bone Healing)
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11 pages, 2296 KiB  
Article
The Effects of Photobiomodulation on Bone Defect Repairing in a Diabetic Rat Model
by Ji-Hua Lee, Su-Chii Kong, Chia-Hsin Chen, Ying-Chun Lin, Kun-Tsung Lee and Yan-Hsiung Wang
Int. J. Mol. Sci. 2021, 22(20), 11026; https://doi.org/10.3390/ijms222011026 - 13 Oct 2021
Cited by 6 | Viewed by 1578
Abstract
The purpose of this study is to examine the prospective therapeutic effects of photobiomodulation on the healing of bone defects in diabetic mellitus (DM) using rat models to provide basic knowledge of photobiomodulation therapy (PBMT) during bone defect repair. For in vitro study, [...] Read more.
The purpose of this study is to examine the prospective therapeutic effects of photobiomodulation on the healing of bone defects in diabetic mellitus (DM) using rat models to provide basic knowledge of photobiomodulation therapy (PBMT) during bone defect repair. For in vitro study, an Alizzarin red stain assay was used to evaluate the effect of PBMT on osteogenic differentiation. For in vivo study, micro-computed tomography (microCT) scan, H&E and IHC stain analysis were used to investigate the effect of PBMT on the healing of the experimental calvarial defect (3 mm in diameter) of a diabetic rat model. For in vitro study, the high glucose groups showed lower osteogenic differentiation in both irradiated and non-irradiated with PBMT when compared to the control groups. With the PBMT, all groups (control, osmotic control and high glucose) showed higher osteogenic differentiation when compared to the non-irradiated groups. For in vivo study, the hyperglycemic group showed significantly lower bone regeneration when compared to the control group. With the PBMT, the volume of bone regeneration was increasing and back to the similar level of the control group. The treatment of PBMT in 660 nm could improve the bone defect healing on a diabetic rat calvarial defect model. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Bone Healing)
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17 pages, 11743 KiB  
Article
Expression of Musashi-1 Increases in Bone Healing
by Miguel Padial-Molina, Vicente Crespo-Lora, Clara Candido-Corral, Nati Martin-Morales, Dario Abril-Garcia, Pablo Galindo-Moreno, Pedro Hernandez-Cortes and Francisco O’Valle
Int. J. Mol. Sci. 2021, 22(7), 3395; https://doi.org/10.3390/ijms22073395 - 26 Mar 2021
Cited by 3 | Viewed by 2511
Abstract
Musashi-1 (MSI1) is an RNA-binding protein that regulates progenitor cells in adult and developing organisms to maintain self-renewal capacities. The role of musashi-1 in the bone healing environment and its relation with other osteogenic factors is unknown. In the current study, we analyze [...] Read more.
Musashi-1 (MSI1) is an RNA-binding protein that regulates progenitor cells in adult and developing organisms to maintain self-renewal capacities. The role of musashi-1 in the bone healing environment and its relation with other osteogenic factors is unknown. In the current study, we analyze the expression of MSI1 in an experimental model of rat femoral bone fractures. We also analyze the relation between MSI1 expression and the expression of two osteogenic markers: periostin (POSTN) and runt-related transcription factor 2 (RUNX2). We use histological, immunohistochemical, and qPCR techniques to evaluate bone healing and the expression of MSI1, POSTN, and RUNX2 over time (4, 7, and 14 days). We compare our findings with non-fractured controls. We find that in bone calluses, the number of cells expressing MSI1 and RUNX2 increase over time and the intensity of POSTN expression decreases over time. Within bone calluses, we find the presence of MSI1 expression in mesenchymal stromal cells, osteoblasts, and osteocytes but not in hypertrophic chondrocytes. After 14 days, the expression of MSI1, POSTN, and RUNX2 was significantly correlated. Thus, we conclude that musashi-1 potentially serves in the osteogenic differentiation of mesenchymal stromal cells and bone healing. Therefore, further studies are needed to determine the possibility of musashi-1′s role as a clinical biomarker of bone healing and therapeutic agent for bone regeneration. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Bone Healing)
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Review

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17 pages, 718 KiB  
Review
Pulsed Electromagnetic Fields in Bone Healing: Molecular Pathways and Clinical Applications
by Laura Caliogna, Marta Medetti, Valentina Bina, Alice Maria Brancato, Alberto Castelli, Eugenio Jannelli, Alessandro Ivone, Giulia Gastaldi, Salvatore Annunziata, Mario Mosconi and Gianluigi Pasta
Int. J. Mol. Sci. 2021, 22(14), 7403; https://doi.org/10.3390/ijms22147403 - 09 Jul 2021
Cited by 35 | Viewed by 6223
Abstract
In this article, we provide an extensive review of the recent literature of the signaling pathways modulated by Pulsed Electromagnetic Fields (PEMFs) and PEMFs clinical application. A review of the literature was performed on two medical electronic databases (PubMed and Embase) from 3 [...] Read more.
In this article, we provide an extensive review of the recent literature of the signaling pathways modulated by Pulsed Electromagnetic Fields (PEMFs) and PEMFs clinical application. A review of the literature was performed on two medical electronic databases (PubMed and Embase) from 3 to 5 March 2021. Three authors performed the evaluation of the studies and the data extraction. All studies for this review were selected following these inclusion criteria: studies written in English, studies available in full text and studies published in peer-reviewed journal. Molecular biology, identifying cell membrane receptors and pathways involved in bone healing, and studying PEMFs target of action are giving a solid basis for clinical applications of PEMFs. However, further biology studies and clinical trials with clear and standardized parameters (intensity, frequency, dose, duration, type of coil) are required to clarify the precise dose-response relationship and to understand the real applications in clinical practice of PEMFs. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Bone Healing)
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14 pages, 297 KiB  
Review
A Review of Recent Developments in the Molecular Mechanisms of Bone Healing
by Emerito Carlos Rodríguez-Merchán
Int. J. Mol. Sci. 2021, 22(2), 767; https://doi.org/10.3390/ijms22020767 - 14 Jan 2021
Cited by 21 | Viewed by 4118
Abstract
Between 5 and 10 percent of fractures do not heal, a condition known as nonunion. In clinical practice, stable fracture fixation associated with autologous iliac crest bone graft placement is the gold standard for treatment. However, some recalcitrant nonunions do not resolve satisfactorily [...] Read more.
Between 5 and 10 percent of fractures do not heal, a condition known as nonunion. In clinical practice, stable fracture fixation associated with autologous iliac crest bone graft placement is the gold standard for treatment. However, some recalcitrant nonunions do not resolve satisfactorily with this technique. For these cases, biological alternatives are sought based on the molecular mechanisms of bone healing, whose most recent findings are reviewed in this article. The pro-osteogenic efficacy of morin (a pale yellow crystalline flavonoid pigment found in old fustic and osage orange trees) has recently been reported, and the combined use of bone morphogenetic protein-9 (BMP9) and leptin might improve fracture healing. Inhibition with methyl-piperidino-pyrazole of estrogen receptor alpha signaling delays bone regeneration. Smoking causes a chondrogenic disorder, aberrant activity of the skeleton’s stem and progenitor cells, and an intense initial inflammatory response. Smoking cessation 4 weeks before surgery is therefore highly recommended. The delay in fracture consolidation in diabetic animals is related to BMP6 deficiency (35 kDa). The combination of bioceramics and expanded autologous human mesenchymal stem cells from bone marrow is a new and encouraging alternative for treating recalcitrant nonunions. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Bone Healing)
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