Pharmacological inhibition of HIF2 protects against bone loss in an experimental model of estrogen deficiency DOI Creative Commons
Giulia Lanzolla, Elena Sabini, Katherine Beigel

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(49)

Published: Nov. 27, 2024

Estrogen deficiency, which is linked to various pathological conditions such as primary ovarian insufficiency and postmenopausal osteoporosis, disrupts the delicate balance between bone formation resorption. This imbalance leads loss an increased risk of fractures, primarily due a significant reduction in trabecular mass. Trabecular osteoblasts, cells responsible for within compartment, originate from skeletal progenitors located marrow. The microenvironment marrow contains hypoxic (low oxygen) regions, hypoxia-inducible factor-2α (HIF2) plays crucial role cellular responses these low-oxygen conditions. study demonstrates that HIF2 their derivatives during development enhances mass by promoting formation. More importantly, PT2399, small molecule specifically inhibits HIF2, effectively prevents ovariectomized adult mice, model estrogen-deficient loss. Both genetic pharmacological approaches result increase osteoblast number, expansion pool progenitor cells. either or inhibition uncovers pivotal mechanism increasing numbers formation, resulting greater

Language: Английский

Skeletal stem and progenitor cells in bone physiology, ageing and disease DOI
Seppe Melis, Dana Trompet, Andrei S. Chagin

et al.

Nature Reviews Endocrinology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 8, 2024

Language: Английский

Citations

7
Innovation in Osteogenesis Activation: Role of Marine-Derived Materials in Bone Regeneration DOI Creative Commons
Maria Giovanna Rizzo, Marilena Briglia, Vincenzo Zammuto

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(3), P. 175 - 175

Published: March 7, 2025

Marine-derived biomaterials are emerging as promising candidates for tissue regeneration due to their sustainability, biocompatibility, bioactivity, and unique chemical structure. This review provides an overview of different marine-derived inorganic organic materials, such calcium carbonate, magnesium salts, silica, polysaccharides, bioactive peptides, lipid-based compounds, effects in promoting osteogenesis. Specifically, the osteoinductive, osteoconductive, osteointegrative activities traditional innovative materials that influence key molecular pathways BMP/Smad Wnt/β-catenin signaling underlying bone formation will be evaluated. also prospects approaches, i.e., phage display technology, optimize peptides targeted regeneration. In context sustainable this suggests some interesting applications unusual able overcome limitations conventional ones stimulate cellular by activating specific pathways.

Language: Английский

Citations

1
Ultrasound‐Driven Innervated Bone Regeneration in Additively Manufactured Degradable Metallic Scaffolds DOI Open Access

Wencheng Song,

Danlei Zhao,

Jiajia Wang

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Abstract Bone tissues are densely innervated by nerve fibers throughout the periosteum and mineralized bone. The impairment of bone regeneration is a critical factor contributing to challenges in osteoporotic remodeling repair. Herein, an “ultrasound‐driven regeneration” strategy proposed additively manufactured degradable Zn‐Cu scaffolds. vitro investigations with RSC96 cells elucidated synergistic promotion low‐intensity pulsed ultrasound (LIPUS) metal cations on Schwann cell proliferation exosome secretion. Notably, these cell‐derived exosomes, once internalized neighboring marrow stromal (BMSCs), significantly enhanced their migration, osteogenic differentiation, extracellular matrix deposition, indicating potent mechanism for regeneration. Furthermore, vivo evaluation validated that LIPUS stimulation activated S100β‐positive facilitated peripheral within cranial defects, leading accelerated healing rats implantation over 2‐ 6‐week recovery periods. This work provides focusing activation enhancement paracrine effect, especially secretion, which further recruited surrounding BMSCs promoted differentiation. study holds considerable promise clinical applications translation treatment defects.

Language: Английский

Citations

1
Stem Cell Recruitment of Bionic Hydrogels Enhances Vascularized Bone Regeneration through Macrophage Reprogramming DOI Creative Commons
Huaiyuan Zhang, Yu Wang, Qiao Wen

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Abstract The local inflammatory microenvironment, insufficient vascularization, and inadequate bone repair materials are the three key factors that constrain of defects. Here, we synthesized a composite nanoparticle, TPQ (TCP-PDA-QK), with core-shell structure. core consists nanotricalcium phosphate (TCP), shell is derived from polydopamine (PDA). surface modified vascular endothelial growth factor (VEGF) mimic peptide (QK peptide). was then embedded in porous methacrylate gelatin (GelMA) to form TPQGel hydrogel. In environment, hydrogel can gradually release drugs through pH responsiveness, promoting M2 macrophage polarization, vascularization regeneration turn. addition, reprogrammed macrophages stimulate generation anti-inflammatory pro-healing factors, which provide additional support for angiogenesis regeneration. not only accurately fill irregular defects but also possesses excellent mechanical properties biocompatibility, making it highly suitable minimally invasive treatment Transcriptomic tests revealed achieved reprogramming by regulating PI3K-AKT signaling pathway. Overall, be harnessed safe efficient therapeutics accelerate

Language: Английский

Citations

0
Cbfβ: A key regulator in skeletal stem cell differentiation, bone development, and disease DOI

Chenggong Zheng,

Chenyang Zhang,

Y.L. He

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(4)

Published: Feb. 25, 2025

Abstract The skeletal system comprises closely related yet functionally distinct bone and cartilage tissues, regulated by a complex network of transcriptional factors signaling molecules. Among these, core‐binding factor subunit beta (Cbfβ) emerges as critical co‐transcriptional that stabilizes Runx proteins, playing indispensable roles in development homeostasis. Emerging evidence from genetic mouse models has highlighted the essential role Cbfβ directing lineage commitment mesenchymal stem cells (MSCs) their differentiation into osteoblasts chondrocytes. Notably, deficiency is strongly associated with severe dysplasia, affecting both endochondral intramembranous ossification during embryonic postnatal development. In this review, we synthesize recent advancements understanding structural molecular functions Cbfβ, particular focus on its interactions key pathways, including BMP/TGF‐β, Wnt/β‐catenin, Hippo/YAP, IHH/PTHrP. These pathways converge Cbfβ/RUNX2 complex, which orchestrates gene expression program for osteogenesis, formation, integration these networks ensures precise regulation development, remodeling, repair. Furthermore, successful local delivery to address abnormalities underscores potential novel therapeutic target disorders such cleidocranial osteoarthritis, metastases. By elucidating mechanisms underlying function insights not only advance our biology but also offer promising avenues clinical intervention, ultimately improving outcomes patients disorders.

Language: Английский

Citations

0
The characterisation and comparison of femoral bone-derived skeletal stem cells DOI Creative Commons
Kayla Howard, William Frank Ferris, Marí van de Vyver

et al.

Biochimie, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Skeletal stem cells (SSCs) reside in various niche locations within long bones to maintain bone homeostasis and facilitate fracture repair. Bone fragility, associated with ageing, increases the susceptibility of femoral head fractures due an increase adipocytes concomitant loss structural integrity. However, specific contribution epiphyseal SSCs fragility is unknown. To explore this, a comparative analysis was performed on transcriptional profiles lineage commitment Wistar rat derived from marrow (BM-), diaphyseal cortical (CB-) proximal trabecular (PF-SSCs) isolated same bones. were characterized based morphology, immunophenotype (CD90/CD45), growth rate (population doubling time), gene expression differentiation capacity (Oil Red O, Alizarin S). qRT-PCR micro-arrays evaluate stemness, SSC lineage-specific markers both undifferentiated differentiated states. Our findings support hypothesis that different regions exhibit distinct profiles, reflecting their environments. CB-SSCs displayed superior osteogenic potential as evidenced by key genes higher levels mineralization. In contrast, PF-SSCs had reduced adipogenic potential. Overall, study revealed importance niche-specific cell properties for use regenerative medicine applications provides insight into role risk.

Language: Английский

Citations

0
Cancer metastasis to the bone: Mechanisms and animal models (Review) DOI Open Access

Meimei Deng,

Hao Ding, Yuru Zhou

et al.

Oncology Letters, Journal Year: 2025, Volume and Issue: 29(5), P. 1 - 12

Published: March 6, 2025

The majority of cancer‑related deaths result from tumor metastasis, with bone metastasis occurring in almost all types malignant tumors. Understanding the mechanism by which tumors metastasize to is critical for identification novel therapeutic targets. A large amount research has been carried out using animal models, and these models have crucial advancing fundamental understanding cancer. However, current are limited; although they can mimic specific stages metastatic process, not able replicate entire process tumorigenesis metastasis. present review describes molecular changes that occur intraosseous microenvironment metastases, including osteolytic osteoblastic types, summarizes advancements

Language: Английский

Citations

0
Callus organoids reveal distinct cartilage to bone transition mechanisms across donors and a role for biological sex DOI Creative Commons
Isaak Decoene, Hanna Svitina, Mohamed Belal Hamed

et al.

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: March 26, 2025

Language: Английский

Citations

0
An injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophages DOI Creative Commons
Huaiyuan Zhang, Yu Wang, Qiao Wen

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 7, 2025

Language: Английский

Citations

0
The bone microenvironment: new insights into the role of stem cells and cell communication in bone regeneration DOI Creative Commons
Luca Dalle Carbonare, Mattia Cominacini, Elisabetta Trabetti

et al.

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

Published: April 12, 2025

Mesenchymal stem cells (MSCs) play a crucial role in bone formation and remodeling. Intrinsic genetic factors extrinsic environmental cues regulate their differentiation into osteoblasts. Within the microenvironment, complex network of biochemical biomechanical signals orchestrates homeostasis regeneration. In addition, crosstalk among MSCs, immune cells, neighboring cells-mediated by extracellular vesicles non-coding RNAs (such as circular micro RNAs) -profoundly influences osteogenic Recent studies have explored specific signaling pathways that contribute to effective regeneration, highlighting potential manipulating microenvironment enhance MSC functionality. The integration advanced biomaterials, gene editing techniques, controlled delivery systems is paving way for more targeted efficient regenerative therapies. Furthermore, artificial intelligence could improve tissue engineering, optimize biomaterial design, enable personalized treatment strategies. This review explores latest advancements emphasizing intricate interplay molecules. By providing comprehensive overview these mechanisms clinical implications, we aim shed light on future research directions this rapidly evolving field.

Language: Английский

Citations

0