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Biomolecules Nov 2021The demand for bone substitutes is increasing in Western countries. Bone graft substitutes aim to provide reconstructive surgeons with off-the-shelf alternatives to the... (Review)
Review
The demand for bone substitutes is increasing in Western countries. Bone graft substitutes aim to provide reconstructive surgeons with off-the-shelf alternatives to the natural bone taken from humans or animal species. Under the tissue engineering paradigm, biomaterial scaffolds can be designed by incorporating bone stem cells to decrease the disadvantages of traditional tissue grafts. However, the effective clinical application of tissue-engineered bone is limited by insufficient neovascularization. As bone is a highly vascularized tissue, new strategies to promote both osteogenesis and vasculogenesis within the scaffolds need to be considered for a successful regeneration. It has been demonstrated that bone and blood vases are piezoelectric, namely, electric signals are locally produced upon mechanical stimulation of these tissues. The specific effects of electric charge generation on different cells are not fully understood, but a substantial amount of evidence has suggested their functional and physiological roles. This review summarizes the special contribution of piezoelectricity as a stimulatory signal for bone and vascular tissue regeneration, including osteogenesis, angiogenesis, vascular repair, and tissue engineering, by considering different stem cell sources entailed with osteogenic and angiogenic potential, aimed at collecting the key findings that may enable the development of successful vascularized bone replacements useful in orthopedic and otologic surgery.
Topics: Bone Regeneration; Osteogenesis; Tissue Engineering; Tissue Scaffolds
PubMed: 34827729
DOI: 10.3390/biom11111731 -
Bone Feb 2021During the past several years, pre-clinical experiments have established that microRNAs (miRNAs), small non-coding RNAs, serve as key regulatory molecules of fracture... (Review)
Review
During the past several years, pre-clinical experiments have established that microRNAs (miRNAs), small non-coding RNAs, serve as key regulatory molecules of fracture healing. Their easy modulation with agonists and antagonists make them highly desirable targets for future therapeutic strategies, especially for pathophysiologic fractures that either do not heal (nonunions) or are delayed. It is now well documented that these problematic fractures lead to human suffering and impairment of life quality. Additionally, financial difficulties are also encountered as work productivity decreases and income is reduced. Moreover, targeting miRNAs may also be an avenue to enhancing normal physiological fracture healing. Herein we present the most current knowledge of the involvement of miRNAs during fracture healing in pre-clinical studies. Following a brief description on the nature of miRNAs and of the fracture healing process, we present data from studies focusing specifically, on miRNA regulation of osteoblast differentiation and osteogenesis (within the context of known signaling pathways), chondrocytes, angiogenesis, and apoptosis, all critical to successful bone repair. Further, we also discuss miRNAs and exosomes. We hope that this manuscript serves as a comprehensive review that will facilitate basic/translational scientists in the orthopaedic arena to realize and further decipher the biological and future therapeutic impact of these small regulatory RNA molecules, especially as they relate to the molecular events of each of the major phases of fracture healing.
Topics: Cell Differentiation; Fracture Healing; Fractures, Bone; Humans; MicroRNAs; Osteogenesis
PubMed: 33212318
DOI: 10.1016/j.bone.2020.115758 -
The American Journal of Pathology Aug 2019Skeletal tissue development and regeneration in mammals are intricate, multistep, and highly regulated processes. Various signaling pathways have been implicated in the... (Review)
Review
Skeletal tissue development and regeneration in mammals are intricate, multistep, and highly regulated processes. Various signaling pathways have been implicated in the regulation of these processes, including Notch. Notch signaling is a highly conserved, intercellular signaling pathway that regulates cell proliferation and differentiation, determines cell fate decision, and participates in cellular process in embryonic and adult tissue. Here, we review recent data showing the regulation of Notch signaling in osteogenesis, osteoclastogenesis, and angiogenesis. These processes are cell-context-dependent via direct or indirect mechanisms. Furthermore, Notch signaling may be highly beneficial for efficient coupling of osteogenesis and angiogenesis for tissue engineering and skeletal repair, which is critical to develop clinically therapeutic options.
Topics: Animals; Cell Differentiation; Cell Proliferation; Humans; Neovascularization, Physiologic; Osteogenesis; Receptors, Notch; Signal Transduction
PubMed: 31345466
DOI: 10.1016/j.ajpath.2019.05.005 -
Proceedings of the National Academy of... May 2023Osteolectin is a recently identified osteogenic growth factor that binds to Integrin α11 (encoded by ), promoting Wnt pathway activation and osteogenic differentiation...
Osteolectin is a recently identified osteogenic growth factor that binds to Integrin α11 (encoded by ), promoting Wnt pathway activation and osteogenic differentiation by bone marrow stromal cells. While and are not required for the formation of the skeleton during fetal development, they are required for the maintenance of adult bone mass. Genome-wide association studies in humans reported a single-nucleotide variant (rs182722517) 16 kb downstream of associated with reduced height and plasma Osteolectin levels. In this study, we tested whether Osteolectin promotes bone elongation and found that -deficient mice have shorter bones than those of sex-matched littermate controls. Integrin α11 deficiency in limb mesenchymal progenitors or chondrocytes reduced growth plate chondrocyte proliferation and bone elongation. Recombinant Osteolectin injections increased femur length in juvenile mice. Human bone marrow stromal cells edited to contain the rs182722517 variant produced less Osteolectin and underwent less osteogenic differentiation than that of control cells. These studies identify Osteolectin/Integrin α11 as a regulator of bone elongation and body length in mice and humans.
Topics: Adult; Mice; Animals; Humans; Chondrocytes; Osteogenesis; Growth Plate; Genome-Wide Association Study; Bone and Bones; Cell Differentiation; Integrins; Cell Proliferation
PubMed: 37216542
DOI: 10.1073/pnas.2220159120 -
Nature Communications Sep 2023The terminal differentiation of osteoblasts and subsequent formation of bone marks an important phase in palate development that leads to the separation of the oral and...
The terminal differentiation of osteoblasts and subsequent formation of bone marks an important phase in palate development that leads to the separation of the oral and nasal cavities. While the morphogenetic events preceding palatal osteogenesis are well explored, major gaps remain in our understanding of the molecular mechanisms driving the formation of this bony union of the fusing palate. Through bulk, single-nucleus, and spatially resolved RNA-sequencing analyses of the developing secondary palate, we identify a shift in transcriptional programming between embryonic days 14.5 and 15.5 pinpointing the onset of osteogenesis. We define spatially restricted expression patterns of key osteogenic marker genes that are differentially expressed between these developmental timepoints. Finally, we identify genes in the palate highly expressed by palate nasal epithelial cells, also enriched within palatal osteogenic mesenchymal cells. This investigation provides a relevant framework to advance palate-specific diagnostic and therapeutic biomarker discovery.
Topics: Transcriptome; Osteogenesis; Gene Expression Profiling; Biomedical Research; Epithelial Cells
PubMed: 37709732
DOI: 10.1038/s41467-023-41349-9 -
International Journal of Molecular... Sep 2022Sufficient oxygen is required to maintain normal cellular and physiological function, such as a creature's development, breeding, and homeostasis. Lately, some... (Review)
Review
Sufficient oxygen is required to maintain normal cellular and physiological function, such as a creature's development, breeding, and homeostasis. Lately, some researchers have reported that both pathological hypoxia and environmental hypoxia might affect bone health. Adaptation to hypoxia is a pivotal cellular event in normal cell development and differentiation and in pathological settings such as ischemia. As central mediators of homeostasis, hypoxia-inducible transcription factors (HIFs) can allow cells to survive in a low-oxygen environment and are essential for the regulation of osteogenesis and skeletal repair. From this perspective, we summarized the role of HIF-1 and HIF-2 in signaling pathways implicated in bone development and skeletal repair and outlined the molecular mechanism of regulation of downstream growth factors and protein molecules such as VEGF, EPO, and so on. All of these present an opportunity for developing therapies for bone regeneration.
Topics: Basic Helix-Loop-Helix Transcription Factors; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Osteogenesis; Oxygen; Transcription Factors; Vascular Endothelial Growth Factor A
PubMed: 36232501
DOI: 10.3390/ijms231911201 -
International Journal of Oral Science Jan 2022Distraction osteogenesis (DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone... (Review)
Review
Distraction osteogenesis (DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.
Topics: Bone Regeneration; Bone and Bones; Osteogenesis; Osteogenesis, Distraction; Tissue Engineering
PubMed: 35067679
DOI: 10.1038/s41368-021-00156-y -
Journal of Cellular and Molecular... Jan 2022Different cellular and molecular mechanisms contribute to chondrocyte and osteocyte development. Although vital roles of the mothers against decapentaplegic homolog 4... (Review)
Review
Different cellular and molecular mechanisms contribute to chondrocyte and osteocyte development. Although vital roles of the mothers against decapentaplegic homolog 4 (also called 'SMAD4') have been discussed in different cancers and stem cell-related studies, there are a few reviews summarizing the roles of this protein in the skeletal development and bone homeostasis. In order to fill this gap, we discuss the critical roles of SMAD4 in the skeletal development. To this end, we review the different signalling pathways and also how SMAD4 defines stem cell features. We also elaborate how the epigenetic factors-ie DNA methylation, histone modifications and noncoding RNAs-make a contribution to the chondrocyte and osteocyte development. To better grasp the important roles of SMAD4 in the cartilage and bone development, we also review the genotype-phenotype correlation in animal models. This review helps us to understand the importance of the SMAD4 in the chondrocyte and bone development and the potential applications for therapeutic goals.
Topics: Animals; Cartilage; Cell Differentiation; Chondrocytes; Chondrogenesis; Osteocytes; Osteogenesis; Signal Transduction; Stem Cells
PubMed: 34841647
DOI: 10.1111/jcmm.17080 -
Mesenchymal stem cells and dental implant osseointegration during aging: from mechanisms to therapy.Stem Cell Research & Therapy Dec 2023Dental implants are widely used to replace missing teeth, providing patients with unparalleled levels of effectiveness, convenience, and affordability. The biological... (Review)
Review
Dental implants are widely used to replace missing teeth, providing patients with unparalleled levels of effectiveness, convenience, and affordability. The biological basis for the clinical success of dental implants is osseointegration. Bone aging is a high-risk factor for the reduced osseointegration and survival rates of dental implants. In aged individuals, mesenchymal stem cells (MSCs) in the bone marrow show imbalanced differentiation with a reduction in osteogenesis and an increase in adipogenesis. This leads to impaired osseointegration and implant failure. This review focuses on the molecular mechanisms underlying the dysfunctional differentiation of aged MSCs, which primarily include autophagy, transcription factors, extracellular vesicle secretion, signaling pathways, epigenetic modifications, microRNAs, and oxidative stress. Furthermore, this review addresses the pathological changes in MSCs that affect osseointegration and discusses potential therapeutic interventions to enhance osseointegration by manipulating the mechanisms underlying MSC aging.
Topics: Humans; Aged; Osseointegration; Dental Implants; Osteogenesis; Aging; Mesenchymal Stem Cells; Surface Properties
PubMed: 38124153
DOI: 10.1186/s13287-023-03611-1 -
Current Osteoporosis Reports Jun 2023Circular RNAs (circRNAs) are RNA transcripts derived from fragments of pre-messenger RNAs through a back-splicing process. An advantage that rises from their circular... (Review)
Review
PURPOSE OF REVIEW
Circular RNAs (circRNAs) are RNA transcripts derived from fragments of pre-messenger RNAs through a back-splicing process. An advantage that rises from their circular covalently closed conformation is their high stability, when compared with their linear counterparts. The current review focuses on the emerging roles of circRNAs in osteoporosis, including in osteogenic differentiation and osteoclastogenesis. Their potential as osteoporosis biomarkers will also be discussed.
RECENT FINDINGS
Although firstly described as non-coding, some of these single-stranded RNAs were recently reported to possess protein-coding capacity. On the other hand, the circRNAs exhibit cell and tissue-specific patterns at the transcriptome level in eukaryotes and are regulated throughout the development or disease progression. Even though thousands of these circular transcripts are listed and annotated, only a limited number of studies describe their biological role in bone processes. Recent evidence indicates inhibitory activator roles in both osteoblasts and osteoclasts differentiation and function. Latest screenings in the blood, plasma, or serum of osteoporosis patients support the potential for circRNA signature to be used as biomarkers in osteoporosis, but further validation is required. While intense research into circRNAs has been detailing their biological roles, there remains a need for standardization and further research to fulfil the future potential of this emerging and highly promising class of regulatory molecules.
Topics: Humans; RNA, Circular; Osteogenesis; RNA; Biomarkers; Osteoporosis
PubMed: 37119447
DOI: 10.1007/s11914-023-00786-7