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The Journal of International Medical... Aug 2023Sclerostin, a protein encoded by the sclerostin () gene, is mostly expressed in osteocytes. First described in the pathogenesis of three disorders, sclerosteosis, van... (Review)
Review
Sclerostin, a protein encoded by the sclerostin () gene, is mostly expressed in osteocytes. First described in the pathogenesis of three disorders, sclerosteosis, van Buchem's disease, and craniodiaphyseal dysplasia, sclerostin has been identified as an important regulator of bone homeostasis, controlling bone formation by osteoblasts through inhibition of the canonical Wnt signaling pathway. Recent studies have highlighted a hypothetical role of sclerostin in myogenesis, thus modulating the interaction between bone and muscle. This narrative review provides an overview of the clinical implications of sclerostin modulation on skeletal muscle mass and function, and bone metabolism. Improving knowledge about muscle-bone crosstalk may represent a turning point in the development of therapeutic strategies for musculoskeletal disorders, particularly osteosarcopenia.
Topics: Humans; Hyperostosis; Knowledge; Muscles; Osteoblasts; Osteogenesis
PubMed: 37632438
DOI: 10.1177/03000605231193293 -
Differentiation; Research in Biological... 2023The vascular system plays a crucial role in bone tissue. Angiogenic and osteogenic processes are coupled through a spatial-temporal connection. Recent studies have... (Review)
Review
The vascular system plays a crucial role in bone tissue. Angiogenic and osteogenic processes are coupled through a spatial-temporal connection. Recent studies have identified three types of capillaries in the skeletal system. Compared with type L and E vessels, type H vessels express high levels of CD31 and endomucin, and function to couple angiogenesis and osteogenesis. Endothelial cells in type H vessels interact with osteolineage cells (e.g., osteoblasts, osteoclasts, and osteocytes) through cytokines or signaling pathways to maintain bone growth and homeostasis. In imbalanced bone homeostases, such as osteoporosis and osteoarthritis, it may be a new therapeutic strategy to regulate the endothelial cell activity in type H vessels to repair the imbalance. Here, we reviewed the latest progress in relevant factors or signaling pathways in coupling angiogenesis and osteogenesis. This review would contribute to further understanding the role and mechanisms of type H vessels in coupling angiogenic and osteogenic processes. Furthermore, it will facilitate the development of therapeutic approaches for bone disorders by targeting type H vessels.
Topics: Osteogenesis; Endothelial Cells; Neovascularization, Physiologic; Bone and Bones; Homeostasis
PubMed: 37774549
DOI: 10.1016/j.diff.2023.09.005 -
Biomaterials Oct 2023Although biodegradable polymer coatings can impede corrosion of magnesium (Mg)-based orthopedic implants, they are prone to excessive degradation and accidental...
Although biodegradable polymer coatings can impede corrosion of magnesium (Mg)-based orthopedic implants, they are prone to excessive degradation and accidental scratching in practice. Bone implant-related infection and limited osteointegration are other factors that adversely impact clinical application of Mg-based biomedical implants. Herein, a self-healing polymeric coating is constructed on the Mg alloy together with incorporation of a stimuli-responsive drug delivery nanoplatform by a spin-spray layer-by-layer (SSLbL) assembly technique. The nanocontainers are based on simvastatin (SIM)-encapsulated hollow mesoporous silica nanoparticles (S@HMSs) modified with polydopamine (PDA) and polycaprolactone diacrylate (PCL-DA) bilayer. Owing to the dynamic reversible reactions, the hybrid coating shows a fast, stable, and cyclical water-enabled self-healing capacity. The antibacterial assay indicates good bacteria-killing properties under near infrared (NIR) irradiation due to synergistic effects of hyperthermia, reactive oxygens species (ROS), and SIM leaching. In vitro results demonstrate that NIR laser irradiation promotes the cytocompatibility, osteogenesis, and angiogenesis. The coating facilitates alkaline phosphatase activity and expedites extracellular matrix mineralization as well as expression of osteogenesis-related genes. This study reveals a useful strategy to develop multifunctional coatings on bioabsorbable Mg alloys for orthopedic implants.
Topics: Osteogenesis; Alloys; Magnesium; Coated Materials, Biocompatible; Bacteria; Hydrogen-Ion Concentration; Corrosion
PubMed: 37467596
DOI: 10.1016/j.biomaterials.2023.122237 -
Frontiers in Bioscience (Landmark... Oct 2023Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells derived from dental pulp that serves as an important model for investigating biological regeneration.... (Review)
Review
Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells derived from dental pulp that serves as an important model for investigating biological regeneration. DPSCs have a multipotent differentiation capacity and can promote different biological processes, including osteogenesis, odontogenesis, chondrogenesis, and angiogenesis. These biological processes are regulated by an extensive range of intra- and extra-cellular factors. Further, biomechanical cues, such as substrate stiffness, physical stress, and cell spreading, have been highlighted as particularly important modulators of DPSC function. This review sought to discuss various related signaling components involved in biomechanical cues and their respective roles in cellular and tissue responses in DPSCs, summarize current findings, and provide an outlook on the potential applications of biomechanics in regenerative medicine and tissue engineering.
Topics: Stem Cells; Dental Pulp; Cell Differentiation; Osteogenesis; Mesenchymal Stem Cells; Cells, Cultured; Cell Proliferation
PubMed: 37919075
DOI: 10.31083/j.fbl2810274 -
Nature Cell Biology Oct 2023
Topics: Osteogenesis; Hematopoiesis
PubMed: 37798544
DOI: 10.1038/s41556-023-01242-5 -
Bone Research Sep 2023Skeletal stem and progenitor cells (SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of...
Skeletal stem and progenitor cells (SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. Single-cell RNA sequencing revealed that Notch signaling becomes elevated in SSPCs during aging. To examine the role of increased Notch activity, we deleted Nicastrin, an essential Notch pathway component, in SSPCs in vivo. Middle-aged conditional knockout mice displayed elevated SSPC osteo-lineage gene expression, increased trabecular bone mass, reduced bone marrow adiposity, and enhanced bone repair. Thus, Notch regulates SSPC cell fate decisions, and moderating Notch signaling ameliorates the skeletal aging phenotype, increasing bone mass even beyond that of young mice. Finally, we identified the transcription factor Ebf3 as a downstream mediator of Notch signaling in SSPCs that is dysregulated with aging, highlighting it as a promising therapeutic target to rejuvenate the aged skeleton.
Topics: Animals; Mice; Osteogenesis; Adipocytes; Adiposity; Aging; Arthrodesis; Mice, Knockout; Psychomotor Agitation
PubMed: 37752132
DOI: 10.1038/s41413-023-00283-8 -
International Journal of Molecular... Sep 2023Bones are constantly exposed to mechanical forces from both muscles and Earth's gravity to maintain bone homeostasis by stimulating bone formation. Mechanotransduction... (Review)
Review
Bones are constantly exposed to mechanical forces from both muscles and Earth's gravity to maintain bone homeostasis by stimulating bone formation. Mechanotransduction transforms external mechanical signals such as force, fluid flow shear, and gravity into intracellular responses to achieve force adaptation. However, the underlying molecular mechanisms on the conversion from mechanical signals into bone formation has not been completely defined yet. In the present review, we provide a comprehensive and systematic description of the mechanotransduction signaling pathways induced by mechanical stimuli during osteogenesis and address the different layers of interconnections between different signaling pathways. Further exploration of mechanotransduction would benefit patients with osteoporosis, including the aging population and postmenopausal women.
Topics: Humans; Female; Aged; Osteogenesis; Mechanotransduction, Cellular; Aging; Gravitation; Homeostasis
PubMed: 37762629
DOI: 10.3390/ijms241814326 -
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... Apr 2024Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided... (Review)
Review
Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided molecular evidence that bone remodeling is under the control of circadian rhythms. Circadian fluctuations have been reported in the serum and urine levels of bone turnover markers, such as digested collagen fragments and bone alkaline phosphatase. Additionally, the expressions of over a quarter of all transcripts in bones show circadian rhythmicity, including the genes encoding master transcription factors for osteoblastogenesis and osteoclastogenesis, osteogenic cytokines, and signaling pathway proteins. Serum levels of calcium, phosphate, parathyroid hormone, and calcitonin also display circadian rhythmicity. Finally, osteoblast- and osteoclast-specific knockout mice targeting the core circadian regulator gene show disrupted bone remodeling, although the results have not always been consistent. Despite these studies, however, establishing a direct link between circadian rhythms and bone remodeling in vivo remains a major challenge. It is nearly impossible to repeatedly collect bone materials from human subjects while following circadian changes. In addition, the differences in circadian gene regulation between diurnal humans and nocturnal mice, the main model organism, remain unclear. Filling the knowledge gap in the circadian regulation of bone remodeling could reveal novel regulatory mechanisms underlying many bone disorders including osteoporosis, genetic diseases, and fracture healing. This is also an important question for the basic understanding of how cell differentiation progresses under the influence of cyclically fluctuating environments.
Topics: Bone Remodeling; Animals; Circadian Rhythm; Humans; Osteoblasts; Osteogenesis; Osteoclasts; Gene Expression Regulation; Bone and Bones
PubMed: 38731934
DOI: 10.3390/ijms25094717 -
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