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Different Strategies for Osteogenic Differentiation and Bone Regeneration

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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 May 2021) | Viewed by 38430

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Special Issue Editor

Prof. Dr. Francesca Paino

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Guest Editor

Department of Biomedical, Surgical and Dental Sciences-University of Milan, Milan, Italy
Interests: mesenchymal stem cells; tissue engineering; osteogenic differentiation; epigenetic modifications in bone regeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Autologous bone graft is the conventional gold standard treatment method for many bone defects. However, bone graft may not be sufficient due to the invasiveness of bone collection and/or limitations in the amount of bone collected from a donor site.

Tissue engineering with the use of mesenchymal stem cells provides an attractive alternative to bone grafting. Combining stem cells, artificial support systems (scaffolds) and biologically active molecules is a promising tool for tissue engineering and, in particular, for bone regeneration. Cell-laden tissue-engineered constructs should have the capability of maintaining proliferation and differentiation.

Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate into mesodermal cell types such as adipocytes, osteocytes and chondrocytes. MSCs are isolated from different tissues including bone marrow, dental pulp, adipose tissue, amniotic fluid and umbilical cord blood.

An ideal scaffold used in tissue engineering for bone regeneration should be biodegradable, biocompatible, bioactive, osteoconductive, and osteoinductive. However, identifying factors and/or biomolecules that stimulate osteogenic differentiation, even through epigenetic modifications, is crucial for the success of bone regeneration. Recently, alternative strategies have been considered in bone regeneration including physical stimuli (i.e., low-power laser irradiation, LPLI).

The aim of this issue is to provide an overview of new studies, as well as updated classical studies. Papers related to any aspect of bone regeneration are welcome.

Prof. Dr. Francesca Paino
Guest Editor

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Keywords

Mesenchymal stem cells
Bone regeneration
Osteogenic differentiation
Biomaterials
Biomolecules
Low-power laser therapy
Growth factors
Osteogenic pathways
Epigenetic modifications

Published Papers (12 papers)

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17 pages, 12462 KiB

Open AccessArticle

Bone Tissue Response to Different Grown Crystal Batches of Octacalcium Phosphate in Rat Long Bone Intramedullary Canal Area

by Yukari Shiwaku, Ryo Hamai, Shinichi Sato, Susumu Sakai, Kaori Tsuchiya, Kazuyoshi Baba, Tetsu Takahashi and Osamu Suzuki

Int. J. Mol. Sci. 2021, 22(18), 9770; https://doi.org/10.3390/ijms22189770 - 09 Sep 2021

Cited by 5 | Viewed by 2157

Abstract

The microstructure of biomaterials influences the cellular and biological responses in the bone. Octacalcium phosphate (OCP) exhibits higher biodegradability and osteoconductivity than hydroxyapatite (HA) during the conversion process from OCP to HA. However, the effect of the microstructure of OCP crystals on long tubular bones has not been clarified. In this study, two types of OCPs with different microstructures, fine-OCP (F-OCP) and coarse-OCP (C-OCP), were implanted in rat tibia for 4 weeks. F-OCP promoted cortical bone regeneration compared with C-OCP. The osteoclasts appearance was significantly higher in the C-OCP group than in the control group (defect only) at 1-week post-implantation. To investigate whether the solubility equilibrium depends on the different particle sizes of OCPs, Nano-OCP, which consisted of nanometer-sized OCPs, was prepared. The degree of supersaturation (DS) tended to decrease modestly in the order of C-OCP, F-OCP, and Nano-OCP with respect to HA and OCP in Tris-HCl buffer. F-OCP showed a higher phosphate ion concentration and lower calcium ion concentration after immersion in the buffer than C-OCP. The crystal structures of both OCPs tended to be converted to HA by rat abdominal implantation. These results suggest that differences in the microstructure of OCPs may affect osteoclastogenesis and result in osteoconductivity of this material in long tubular bone by altering dissolution behavior. Full article

(This article belongs to the Special Issue Different Strategies for Osteogenic Differentiation and Bone Regeneration)

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15 pages, 5715 KiB

Open AccessArticle

Performance of the Polydopamine-Graphene Oxide Composite Substrate in the Osteogenic Differentiation of Mouse Embryonic Stem Cells

by Na Young Shim and Jung Sun Heo

Int. J. Mol. Sci. 2021, 22(14), 7323; https://doi.org/10.3390/ijms22147323 - 07 Jul 2021

Cited by 10 | Viewed by 2092

Abstract

Graphene oxide (GO) is a biocompatible material considered a favorable stem cell culture substrate. In this study, GO was modified with polydopamine (PDA) to facilitate depositing GO onto a tissue culture polystyrene (PT) surface, and the osteogenic performance of the PDA/GO composite in pluripotent embryonic stem cells (ESCs) was investigated. The surface chemistry of the PDA/GO-coated PT surface was analyzed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). A high cell viability of ESCs cultured on the PDA/GO composite-coated surface was initially ensured. Then, the osteogenic differentiation of the ESCs in response to the PDA/GO substrate was assessed by alkaline phosphatase (ALP) activity, intracellular calcium levels, matrix mineralization assay, and evaluation of the mRNA and protein levels of osteogenic factors. The culture of ESCs on the PDA/GO substrate presented higher osteogenic potency than that on the uncoated control surface. ESCs cultured on the PDA/GO substrate expressed significantly higher levels of integrin α5 and β1, as well as bone morphogenetic protein receptor (BMPR) types I and II, compared with the control groups. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38, and c-Jun-N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) was observed in ESCs culture on the PDA/GO substrate. Moreover, BMP signal transduction by SMAD1/5/8 phosphorylation was increased more in cells on PDA/GO than in the control. The nuclear translocation of SMAD1/5/8 in cells was also processed in response to the PDA/GO substrate. Blocking activation of the integrin α5/β1, MAPK, or SMAD signaling pathways downregulated the PDA/GO-induced osteogenic differentiation of ESCs. These results suggest that the PDA/GO composite stimulates the osteogenic differentiation of ESCs via the integrin α5/β1, MAPK, and BMPR/SMAD signaling pathways. Full article

(This article belongs to the Special Issue Different Strategies for Osteogenic Differentiation and Bone Regeneration)

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15 pages, 3652 KiB

Open AccessArticle

Exposure to 16 Hz Pulsed Electromagnetic Fields Protect the Structural Integrity of Primary Cilia and Associated TGF-β Signaling in Osteoprogenitor Cells Harmed by Cigarette Smoke

by Yangmengfan Chen, Romina H. Aspera-Werz, Maximilian M. Menger, Karsten Falldorf, Michael Ronniger, Christina Stacke, Tina Histing, Andreas K. Nussler and Sabrina Ehnert

Int. J. Mol. Sci. 2021, 22(13), 7036; https://doi.org/10.3390/ijms22137036 - 29 Jun 2021

Cited by 9 | Viewed by 2176

Abstract

Cigarette smoking (CS) is one of the main factors related to avoidable diseases and death across the world. Cigarette smoke consists of numerous toxic compounds that contribute to the development of osteoporosis and fracture nonunion. Exposure to pulsed electromagnetic fields (PEMF) was proven to be a safe and effective therapy to support bone fracture healing. The aims of this study were to investigate if extremely low frequency (ELF-) PEMFs may be beneficial to treat CS-related bone disease, and which effect the duration of the exposure has. In this study, immortalized human mesenchymal stem cells (SCP-1 cells) impaired by 5% cigarette smoke extract (CSE) were exposed to ELF-PEMFs (16 Hz) with daily exposure ranging from 7 min to 90 min. Cell viability, adhesion, and spreading were evaluated by Sulforhodamine B, Calcein-AM staining, and Phalloidin-TRITC/Hoechst 33342 staining. A migration assay kit was used to determine cell migration. Changes in TGF-β signaling were evaluated with an adenoviral Smad2/3 reporter assay, RT-PCR, and Western blot. The structure and distribution of primary cilia were analyzed with immunofluorescent staining. Our data indicate that 30 min daily exposure to a specific ELF-PEMF most effectively promoted cell viability, enhanced cell adhesion and spreading, accelerated migration, and protected TGF-β signaling from CSE-induced harm. In summary, the current results provide evidence that ELF-PEMF can be used to support early bone healing in patients who smoke. Full article

(This article belongs to the Special Issue Different Strategies for Osteogenic Differentiation and Bone Regeneration)

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16 pages, 4064 KiB

Open AccessArticle

Screen Key Genes Associated with Distraction-Induced Osteogenesis of Stem Cells Using Bioinformatics Methods

by Jishizhan Chen, Jia Hua and Wenhui Song

Int. J. Mol. Sci. 2021, 22(12), 6505; https://doi.org/10.3390/ijms22126505 - 17 Jun 2021

Cited by 2 | Viewed by 2150

Abstract

Background: Applying mesenchymal stem cells (MSCs), together with the distraction osteogenesis (DO) process, displayed enhanced bone quality and shorter treatment periods. The DO guides the differentiation of MSCs by providing mechanical clues. However, the underlying key genes and pathways are largely unknown. The aim of this study was to screen and identify hub genes involved in distraction-induced osteogenesis of MSCs and potential molecular mechanisms. Material and Methods: The datasets were downloaded from the ArrayExpress database. Three samples of negative control and two samples subjected to 5% cyclic sinusoidal distraction at 0.25 Hz for 6 h were selected for screening differentially expressed genes (DEGs) and then analysed via bioinformatics methods. The Gene Ontology (GO) terms and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment were investigated. The protein–protein interaction (PPI) network was visualised through the Cytoscape software. Gene set enrichment analysis (GSEA) was conducted to verify the enrichment of a self-defined osteogenic gene sets collection and identify osteogenic hub genes. Results: Three hub genes (IL6, MMP2, and EP300) that were highly associated with distraction-induced osteogenesis of MSCs were identified via the Venn diagram. These hub genes could provide a new understanding of distraction-induced osteogenic differentiation of MSCs and serve as potential gene targets for optimising DO via targeted therapies. Full article

(This article belongs to the Special Issue Different Strategies for Osteogenic Differentiation and Bone Regeneration)

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18 pages, 4184 KiB

Open AccessArticle

Osteogenic Potential of Mesenchymal Stem Cells from Adipose Tissue, Bone Marrow and Hair Follicle Outer Root Sheath in a 3D Crosslinked Gelatin-Based Hydrogel

by Hanluo Li, Hafiz Awais Nawaz, Federica Francesca Masieri, Sarah Vogel, Ute Hempel, Alexander K. Bartella, Rüdiger Zimmerer, Jan-Christoph Simon, Michaela Schulz-Siegmund, Michael Hacker, Bernd Lethaus and Vuk Savković

Int. J. Mol. Sci. 2021, 22(10), 5404; https://doi.org/10.3390/ijms22105404 - 20 May 2021

Cited by 3 | Viewed by 3304

Abstract

Bone transplantation is regarded as the preferred therapy to treat a variety of bone defects. Autologous bone tissue is often lacking at the source, and the mesenchymal stem cells (MSCs) responsible for bone repair mechanisms are extracted by invasive procedures. This study explores the potential of autologous mesenchymal stem cells derived from the hair follicle outer root sheath (MSCORS). We demonstrated that MSCORS have a remarkable capacity to differentiate in vitro towards the osteogenic lineage. Indeed, when combined with a novel gelatin-based hydrogel called Osteogel, they provided additional osteoinductive cues in vitro that may pave the way for future application in bone regeneration. MSCORS were also compared to MSCs from adipose tissue (ADMSC) and bone marrow (BMMSC) in a 3D Osteogel model. We analyzed gel plasticity, cell phenotype, cell viability, and differentiation capacity towards the osteogenic lineage by measuring alkaline phosphatase (ALP) activity, calcium deposition, and specific gene expression. The novel injectable hydrogel filled an irregularly shaped lesion in a porcine wound model displaying high plasticity. MSCORS in Osteogel showed a higher osteo-commitment in terms of calcium deposition and expression dynamics of OCN, BMP2, and PPARG when compared to ADMSC and BMMSC, whilst displaying comparable cell viability and ALP activity. In conclusion, autologous MSCORS combined with our novel gelatin-based hydrogel displayed a high capacity for differentiation towards the osteogenic lineage and are acquired by non-invasive procedures, therefore qualifying as a suitable and expandable novel approach in the field of bone regeneration therapy. Full article

(This article belongs to the Special Issue Different Strategies for Osteogenic Differentiation and Bone Regeneration)

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17 pages, 3848 KiB

Open AccessArticle

An Intermediate Concentration of Calcium with Antioxidant Supplement in Culture Medium Enhances Proliferation and Decreases the Aging of Bone Marrow Mesenchymal Stem Cells

by Chung-Da Yang, Shu-Chun Chuang, Tsung-Lin Cheng, Mon-Juan Lee, Hui-Ting Chen, Sung-Yen Lin, Hsuan-Ti Huang, Cheng-Jung Ho, Yi-Shan Lin, Lin Kang, Mei-Ling Ho, Je-Ken Chang and Chung-Hwan Chen

Int. J. Mol. Sci. 2021, 22(4), 2095; https://doi.org/10.3390/ijms22042095 - 20 Feb 2021

Cited by 4 | Viewed by 2404

Abstract

Human bone marrow stem cells (HBMSCs) are isolated from the bone marrow. Stem cells can self-renew and differentiate into various types of cells. They are able to regenerate kinds of tissue that are potentially used for tissue engineering. To maintain and expand these cells under culture conditions is difficult—they are easily triggered for differentiation or death. In this study, we describe a new culture formula to culture isolated HBMSCs. This new formula was modified from NCDB 153, a medium with low calcium, supplied with 5% FBS, extra growth factor added to it, and supplemented with N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate to maintain the cells in a steady stage. The cells retain these characteristics as primarily isolated HBMSCs. Moreover, our new formula keeps HBMSCs with high proliferation rate and multiple linage differentiation ability, such as osteoblastogenesis, chondrogenesis, and adipogenesis. It also retains HBMSCs with stable chromosome, DNA, telomere length, and telomerase activity, even after long-term culture. Senescence can be minimized under this new formulation and carcinogenesis of stem cells can also be prevented. These modifications greatly enhance the survival rate, growth rate, and basal characteristics of isolated HBMSCs, which will be very helpful in stem cell research. Full article

(This article belongs to the Special Issue Different Strategies for Osteogenic Differentiation and Bone Regeneration)

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13 pages, 2481 KiB

Open AccessArticle

Tranexamic Acid Promotes Murine Bone Marrow-Derived Osteoblast Proliferation and Inhibits Osteoclast Formation In Vitro

by Anke Baranowsky, Jessika Appelt, Kristina Tseneva, Shan Jiang, Denise Jahn, Serafeim Tsitsilonis, Karl-Heinz Frosch and Johannes Keller

Int. J. Mol. Sci. 2021, 22(1), 449; https://doi.org/10.3390/ijms22010449 - 05 Jan 2021

Cited by 7 | Viewed by 2307

Abstract

Despite modern surgical trauma care, bleeding contributes to one-third of trauma-related death. A significant improvement was obtained through the introduction of tranexamic acid (TXA), which today is widely used in emergency and elective orthopedic surgery to control bleeding. However, concerns remain regarding potential adverse effects on bone turnover and regeneration. Therefore, we employed standardized cell culture systems including primary osteoblasts, osteoclasts, and macrophages to evaluate potential effects of TXA on murine bone cells. While osteoblasts derived from calvarial digestion were not affected, TXA increased cell proliferation and matrix mineralization in bone marrow-derived osteoblasts. Short-term TXA treatment (6 h) failed to alter the expression of osteoblast markers; however, long-term TXA stimulation (10 days) was associated with the increased expression of genes involved in osteoblast differentiation and extracellular matrix synthesis. Similarly, whereas short-term TXA treatment did not affect gene expression in terminally differentiated osteoclasts, long-term TXA stimulation resulted in the potent inhibition of osteoclastogenesis. Finally, in bone marrow-derived macrophages activated with LPS, simultaneous TXA treatment led to a reduced expression of inflammatory cytokines and chemokines. Collectively, our study demonstrates a differential action of TXA on bone cells including osteoanabolic, anti-resorptive, and anti-inflammatory effects in vitro which suggests novel treatment applications. Full article

(This article belongs to the Special Issue Different Strategies for Osteogenic Differentiation and Bone Regeneration)

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17 pages, 2464 KiB

Open AccessArticle

Burst, Short, and Sustained Vitamin D₃ Applications Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells

by Cindy Kelder, Jolanda M.A. Hogervorst, Daniël Wismeijer, Cornelis J. Kleverlaan, Teun J. de Vries and Astrid D. Bakker

Int. J. Mol. Sci. 2020, 21(9), 3202; https://doi.org/10.3390/ijms21093202 - 30 Apr 2020

Cited by 2 | Viewed by 2129

Abstract

Incorporation of 1,25(OH)₂ vitamin D₃ (vitD₃) into tissue-engineered scaffolds could aid the healing of critical-sized bone defects. We hypothesize that shorter applications of vitD₃ lead to more osteogenic differentiation of mesenchymal stem cells (MSCs) than a sustained application. To test this, release from a scaffold was mimicked by exposing MSCs to exactly controlled vitD₃ regimens. Human adipose stem cells (hASCs) were seeded onto calcium phosphate particles, cultured for 20 days, and treated with 124 ng vitD₃, either provided during 30 min before seeding ([200 nM]), during the first two days ([100 nM]), or during 20 days ([10 nM]). Alternatively, hASCs were treated for two days with 6.2 ng vitD₃ ([10 nM]). hASCs attached to the calcium phosphate particles and were viable (~75%). Cell number was not affected by the various vitD₃ applications. VitD₃ (124 ng) applied over 20 days increased cellular alkaline phosphatase activity at Days 7 and 20, reduced expression of the early osteogenic marker RUNX2 at Day 20, and strongly upregulated expression of the vitD₃ inactivating enzyme CYP24. VitD₃ (124 ng) also reduced RUNX2 and increased CYP24 applied at [100 nM] for two days, but not at [200 nM] for 30 min. These results show that 20-day application of vitD₃ has more effect on hASCs than the same total amount applied in a shorter time span. Full article

(This article belongs to the Special Issue Different Strategies for Osteogenic Differentiation and Bone Regeneration)

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10 pages, 3024 KiB

Open AccessCommunication

A Comparative In Vitro Analysis of the Osteogenic Potential of Human Dental Pulp Stem Cells Using Various Differentiation Conditions

by Terezia Okajcekova, Jan Strnadel, Michal Pokusa, Romana Zahumenska, Maria Janickova, Erika Halasova and Henrieta Skovierova

Int. J. Mol. Sci. 2020, 21(7), 2280; https://doi.org/10.3390/ijms21072280 - 26 Mar 2020

Cited by 19 | Viewed by 3377

Abstract

Dental pulp stem cells (DPSCs) have excellent proliferative properties, mineralization potential and can be easily obtained from third molar teeth. Recently, many studies have focused on isolation and differentiation of DPSCs. In our study, we focused on biological properties of non-differentiated DPSCs in comparison with osteogenic differentiated cells from DPSCs. We analyzed morphology as well as mineralization potential using three varied osteogenic differentiation media. After fifteen days of differentiation, calcium deposit production was observed in all three osteogenic differentiation media. However, only one osteogenic medium, without animal serum supplement, showed rapid and strong calcification—OsteoMAX-XF™ Differentiation Medium. Therefore, we examined specific surface markers, and gene and protein expression of cells differentiated in this osteogenic medium, and compared them to non-differentiated DPSCs. We proved a decrease in expression of CD9 and CD90 mesenchymal stem cell surface markers, as well as downregulation in the expression of pluripotency genes (NANOG and OCT-4) and increased levels of expression in osteogenic genes (ALP, BSP, OCN and RUNX2). Moreover, osteogenic proteins, such as BSP and OCN, were only produced in differentiated cells. Our findings confirm that carefully selected differentiation conditions for stem cells are essential for their translation into future clinical applications. Full article

(This article belongs to the Special Issue Different Strategies for Osteogenic Differentiation and Bone Regeneration)

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17 pages, 2790 KiB

Open AccessArticle

Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression

by Zhihao Chen, Yan Zhang, Fan Zhao, Chong Yin, Chaofei Yang, Xue Wang, Zixiang Wu, Shujing Liang, Dijie Li, Xiao Lin, Ye Tian, Lifang Hu, Yu Li and Airong Qian

Int. J. Mol. Sci. 2020, 21(4), 1259; https://doi.org/10.3390/ijms21041259 - 13 Feb 2020

Cited by 40 | Viewed by 4071

Abstract

Background: Irisin, a novel exercise-induced myokine, was shown to mediate beneficial effects of exercise in osteoporosis. Microgravity is a major threat to bone homeostasis of astronauts during long-term spaceflight, which results in decreased bone formation. Methods: The hind-limb unloading mice model and a random position machine are respectively used to simulate microgravity in vivo and in vitro. Results: We demonstrate that not only are bone formation and osteoblast differentiation decreased, but the expression of fibronectin type III domain-containing 5 (Fdnc5; irisin precursor) is also downregulated under simulated microgravity. Moreover, a lower dose of recombinant irisin (r-irisin) (1 nM) promotes osteogenic marker gene (alkaline phosphatase (Alp), collagen type 1 alpha-1(ColIα1)) expressions, ALP activity, and calcium deposition in primary osteoblasts, with no significant effect on osteoblast proliferation. Furthermore, r-irisin could recover the decrease in osteoblast differentiation induced by simulated microgravity. We also find that r-irisin increases β-catenin expression and partly neutralizes the decrease in β-catenin expression induced by simulated microgravity. In addition, β-catenin overexpression could also in part attenuate osteoblast differentiation reduction induced by simulated microgravity. Conclusions: The present study is the first to show that r-irisin positively regulates osteoblast differentiation under simulated microgravity through increasing β-catenin expression, which may reveal a novel mechanism, and it provides a prevention strategy for bone loss and muscle atrophy induced by microgravity. Full article

(This article belongs to the Special Issue Different Strategies for Osteogenic Differentiation and Bone Regeneration)

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Review

Jump to: Research

26 pages, 1404 KiB

Open AccessReview

Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration

by Iratxe Macías, Natividad Alcorta-Sevillano, Arantza Infante and Clara I. Rodríguez

Int. J. Mol. Sci. 2021, 22(14), 7724; https://doi.org/10.3390/ijms22147724 - 20 Jul 2021

Cited by 14 | Viewed by 4324

Abstract

Bone damage leading to bone loss can arise from a wide range of causes, including those intrinsic to individuals such as infections or diseases with metabolic (diabetes), genetic (osteogenesis imperfecta), and/or age-related (osteoporosis) etiology, or extrinsic ones coming from external insults such as trauma or surgery. Although bone tissue has an intrinsic capacity of self-repair, large bone defects often require anabolic treatments targeting bone formation process and/or bone grafts, aiming to restore bone loss. The current bone surrogates used for clinical purposes are autologous, allogeneic, or xenogeneic bone grafts, which although effective imply a number of limitations: the need to remove bone from another location in the case of autologous transplants and the possibility of an immune rejection when using allogeneic or xenogeneic grafts. To overcome these limitations, cutting edge therapies for skeletal regeneration of bone defects are currently under extensive research with promising results; such as those boosting endogenous bone regeneration, by the stimulation of host cells, or the ones driven exogenously with scaffolds, biomolecules, and mesenchymal stem cells as key players of bone healing process. Full article

(This article belongs to the Special Issue Different Strategies for Osteogenic Differentiation and Bone Regeneration)

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13 pages, 1274 KiB

Open AccessReview

The Influence of Strontium on Bone Tissue Metabolism and Its Application in Osteoporosis Treatment

by Barbara Kołodziejska, Natalia Stępień and Joanna Kolmas

Int. J. Mol. Sci. 2021, 22(12), 6564; https://doi.org/10.3390/ijms22126564 - 18 Jun 2021

Cited by 112 | Viewed by 6704

Abstract

Osteoporosis is a chronic disease characterized by low bone mass caused by increased bone turnover and impaired bone microarchitecture. In treatment, we use antiresorptive or anabolic drugs, which usually have a unidirectional effect, i.e., they inhibit the activity of osteoclasts or stimulate the effect of osteoblasts. Strontium ranelate is an anti-osteoporosis drug with a unique mechanism of action (used primarily in postmenopausal women). Unlike other medicines, it has a multidirectional effect on bone tissue, intensifying osteoblastogenesis while inhibiting osteoclastogenesis. It turns out that this effect is demonstrated by strontium ions, an element showing physical and chemical similarity to calcium, the basic element that builds the mineral fraction of bone. As a result, strontium acts through the calcium-sensing receptor (CaSR) receptor in bone tissue cells. In recent years, there has been a significant increase in interest in the introduction of strontium ions in place of calcium ions in ceramics used as bone replacement materials for the treatment of bone fractures and defects caused by osteoporosis. The aim of this study was to summarize current knowledge about the role of strontium in the treatment of osteoporosis, its effects (in various forms), and the ways in which it is administered. Full article

(This article belongs to the Special Issue Different Strategies for Osteogenic Differentiation and Bone Regeneration)

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