Application of dental pulp stem cells for bone regeneration

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Feb. 29, 2024

Bone defects resulting from severe trauma, tumors, inflammation, and other factors are increasingly prevalent. Stem cell-based therapies have emerged as a promising alternative. Dental pulp stem cells (DPSCs), sourced dental pulp, garnered significant attention owing to their ready accessibility minimal collection-associated risks. Ongoing investigations into DPSCs revealed potential undergo osteogenic differentiation capacity secrete diverse array of ontogenetic components, such extracellular vesicles cell lysates. This comprehensive review article aims provide an in-depth analysis secretory emphasizing extraction techniques utilization while elucidating the intricate mechanisms governing bone regeneration. Furthermore, we explore merits demerits cell-free therapeutic modalities, well discuss prospects, opportunities, inherent challenges associated with DPSC therapy in context

Language: Английский

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Induction of osteogenesis by bone-targeted Notch activation

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Feb. 4, 2022

Declining bone mass is associated with aging and osteoporosis, a disease characterized by progressive weakening of the skeleton increased fracture incidence. Growth lifelong homeostasis rely on interactions between different cell types including vascular cells mesenchymal stromal (MSCs). As these involve Notch signaling, we have explored whether treatment secreted ligand proteins can enhance osteogenesis in adult mice. We show that bone-targeting, high affinity version Delta-like 4, termed Dll4 (E12) , induces formation male mice without causing adverse effects other organs, which are known to intact signaling. Due lower surface thereby reduced retention same approach failed promote female ovariectomized but strongly enhanced trabecular combination parathyroid hormone. Single analysis indicates primarily acts MSCs has comparably minor osteoblasts, endothelial cells, or chondrocytes. propose activation signaling bone-targeted fusion might be therapeutically useful avoid detrimental Notch-dependent processes organs.

Language: Английский

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Jiangu granules ameliorate postmenopausal osteoporosis via rectifying bone homeostasis imbalance: A network pharmacology analysis based on multi-omics validation

Phytomedicine, Journal Year: 2023, Volume and Issue: 122, P. 155137 - 155137

Published: Oct. 5, 2023

Language: Английский

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Exosomes: A New Hope for Angiogenesis-Mediated Bone Regeneration

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5204 - 5204

Published: May 10, 2024

Bone is a metabolically dynamic structure that generally remodeled throughout the lifetime of an individual but often causes problems with increasing age. A key player for bone development and homeostasis, also under pathological conditions, vasculature. This complex system arteries, veins, capillaries forms distinct structures where each subset endothelial cells has important functions. Starting basic process angiogenesis bone-specific blood vessel formation, coupled initial importance different vascular highlighted respect to how these are maintained or changed during aging, conditions. After exemplifying current knowledge on vasculature, this review will move exosomes, novel hotspot scientific research. Exosomes be introduced starting from their discovery via isolation procedures state-of-the-art characterization role in development, regeneration repair while summarizing underlying signal transduction pathways. With processes, especially mesenchymal stem cell-derived extracellular vesicles interest, which leads discussion patented applications update ongoing clinical trials. Taken together, provides overview vasculature regeneration, major focus exosomes influence intricate system, as they might useful therapeutic purposes near future.

Language: Английский

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Targeting type H vessels in bone‐related diseases

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(4)

Published: Feb. 1, 2024

Blood vessels are essential for bone development and metabolism. Type H in bone, named after their high expression of CD31 Endomucin (Emcn), have recently been reported to locate mainly the metaphysis, exhibit different molecular properties couple osteogenesis angiogenesis. A strong correlation between type metabolism is now well-recognized. The crosstalk osteoprogenitor cells also involved metabolism-related diseases such as osteoporosis, osteoarthritis, fracture healing defects. Targeting vessel formation may become a new approach managing variety diseases. This review highlighted roles bone-related summarized research attempts develop targeted intervention, which will help us gain better understanding potential value clinical application.

Language: Английский

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Endothelial to mesenchymal Notch signaling regulates skeletal repair

JCI Insight, Journal Year: 2024, Volume and Issue: 9(12)

Published: May 23, 2024

We present a transcriptomic analysis that provides better understanding of regulatory mechanisms within the healthy and injured periosteum. The focus this work is on characterizing early events controlling bone healing during formation periosteal callus day 3 after fracture. Building our previous findings showing induced Notch1 signaling in osteoprogenitors leads to healing, we compared samples which Notch 1 intracellular domain overexpressed by stem/progenitor cells, with control intact fractured Molecular changes skeletal cells (SSPCs) other cell populations callus, including hematopoietic lineages, were determined. Notably, ligands differentially expressed endothelial mesenchymal populations, Dll4 restricted whereas Jag1 was populations. Targeted deletion using Cdh5CreER resulted negative effects fracture while SSPCs α-smooth muscle actin-CreER did not impact healing. Translating these observations into clinically relevant model revealed beneficial delivering alongside osteogenic inducer, BMP2. These provide insights periosteum, paving way for novel translational approaches

Language: Английский

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Notch signaling and fluid shear stress in regulating osteogenic differentiation

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: Oct. 5, 2022

Osteoporosis is a common bone and metabolic disease that characterized by density loss microstructural degeneration. Human marrow-derived mesenchymal stem cells (hMSCs) are multipotent progenitor with the potential to differentiate into various cell types, including osteoblasts, chondrocytes, adipocytes, which have been utilized extensively in field of tissue engineering cell-based therapy. Although fluid shear stress plays an important role osteogenic differentiation, cellular molecular mechanisms underlying this effect remain poorly understood. Here, locked nucleic acid (LNA)/DNA nanobiosensor was exploited monitor mRNA gene expression hMSCs were exposed physiologically relevant examine regulatory Notch signaling during differentiation. First, effects on viability, proliferation, morphology, differentiation investigated compared. Our results showed modulates morphology depending applied duration. By incorporating LNA/DNA alkaline phosphatase (ALP) staining, we further regulating Pharmacological treatment disrupt investigate govern induced experimental provide convincing evidence supporting regulates through signaling. Inhibition mediates reduced ALP enzyme activity decreased Dll4 expression. In conclusion, our will add new information concerning under Further studies may elucidate mechanosensitive

Language: Английский

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Sphingosine-1-phosphate promotes osteogenesis by stimulating osteoblast growth and neovascularization in a vascular endothelial growth factor–dependent manner

Journal of Bone and Mineral Research, Journal Year: 2024, Volume and Issue: 39(3), P. 357 - 372

Published: Jan. 24, 2024

Sphingosine-1-phosphate (S1P) plays multiple roles in bone metabolism and regeneration. Here, we have identified a novel S1P-regulated osteoanabolic mechanism functionally connecting osteoblasts (OBs) to the highly specialized vasculature. We demonstrate that S1P/S1PR3 signaling OBs stimulates vascular endothelial growth factor (VEGFa) expression secretion promote an autocrine boost osteogenic H-type differentiation of marrow cells paracrine manner. VEGFa-neutralizing antibodies VEGF receptor inhibition by axitinib abrogated OB vitro formation male C57BL/6J vivo following S1P stimulation lyase inhibition, respectively. Pharmacological S1PR3 genetic deficiency suppressed VEGFa production, vitro, inhibited angiogenesis mice vivo. Together with previous work on functions S1PR2 S1PR3, our data suggest S1P-dependent regeneration employs several nonredundant positive feedback loops between The identification this yet unappreciated aspect may implications for regular homeostasis as well diseases where microvasculature is affected such age-related osteopenia posttraumatic

Language: Английский

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Fluorescein-based SynNotch adaptors for regulating gene expression responses to diverse extracellular and matrix-based cues

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 20, 2025

Synthetic Notch (SynNotch) receptors function like natural proteins and can be used to install customized sense-and-respond capabilities into mammalian cells. Here, we introduce an adaptor-based strategy for regulating SynNotch activity via fluorescein isomers analogs. Using optimized fluorescein-binding receptor, describe ways chemically control signaling, including approach based on a bio-orthogonal chemical ligation spatially controllable the photo-patterned uncaging of o-nitrobenzyl-caged conjugate. We further show that fluorescein-conjugated extracellular matrix (ECM)-binding peptides regulate depending folding state collagen-based ECM networks. To demonstrate utility these tools, apply them activate dose-dependent gene expression responses induce myogenic-like phenotypes in multipotent fibroblasts with spatiotemporal microenvironmental control. Overall, as versatile tool transcriptional ligands clinically-approved dye. endow cells custom capabilities. authors controlling diverse stimuli fluorescein-conjugates.

Language: Английский

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Communication between endothelial cells and osteoblasts in regulation of bone homeostasis: Notch players

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 7, 2025

Endothelial cells coat blood vessels and release molecular signals to affect the fate of other cells. can adjust their behavior in response changing microenvironmental conditions. During bone regeneration, tissue factors that promote vessel growth. Notch is a key signaling regulates cell decisions many tissues plays an important role development homeostasis. Understanding interplay between angiogenesis osteogenesis currently focus research efforts order facilitate improve when needed. Our review explores cellular mechanisms including Notch-dependent endothelial-MSC communication drive osteogenesis-angiogenesis processes effects on remodeling repair.

Language: Английский

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