Targeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow DOI Open Access
Tongling Huang,

Zhaocheng Lu,

Zihui Wang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 14, 2023

Abstract Ectopic bone marrow adipocytes (BMAds) accumulation occurring under diverse pathophysiological conditions leads to deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency rescues osteogenesis and vascular formation in adipocyte-rich due estrogen or obesity. Mechanistically, adipocyte interferes with E2/ESR1 signaling resulting transcriptional repression of secreted phosphoprotein 1 ( Spp1 ); positively modulates Leptin expression by binding its promoter. abrogation results enhanced SPP1 decreased LEPTIN secretion from both visceral BMAds, concertedly dictating stromal stem cell fate commitment restoring type H vessel formation, constituting feed-forward loop for formation. Pharmacological inhibition protects obese mice against loss high adiposity. Thus, our findings highlight therapeutic approach via targeting preserve especially detrimental milieu. Graphic abstract

Language: Английский

Enhancer hijacking at the ARHGAP36 locus is associated with connective tissue to bone transformation DOI Creative Commons
Uirá Souto Melo, Jerome Jatzlau, Cesar A. Prada‐Medina

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 11, 2023

Heterotopic ossification is a disorder caused by abnormal mineralization of soft tissues in which signaling pathways such as BMP, TGFβ and WNT are known key players driving ectopic bone formation. Identifying novel genes related to the process important steps for future gene therapy disorders. In this study, we detect an inter-chromosomal insertional duplication female proband disrupting topologically associating domain causing ultra-rare progressive form heterotopic ossification. This structural variant lead enhancer hijacking misexpression ARHGAP36 fibroblasts, validated here orthogonal vitro studies. addition, overexpression inhibits TGFβ, activates hedgehog genes/proteins extracellular matrix production. Our work on genetic cause case has revealed that plays role formation metabolism, outlining first details contributing bone-formation -disease.

Language: Английский

Citations

8
Exploring calcium-free alternatives in endochondral bone repair tested on In vivo trials - A review DOI Creative Commons
William Cárdenas-Aguazaco, Adriana Lara-Bertrand, Leonardo Prieto-Abello

et al.

Regenerative Therapy, Journal Year: 2024, Volume and Issue: 26, P. 145 - 160

Published: June 1, 2024

Bone repair via endochondral ossification is a complex process for the critical size reparation of bone defects. Tissue engineering strategies are being developed as alternative treatments to autografts or allografts. Most approaches regeneration involve use calcium composites. However, exploring calcium-free alternatives in has emerged promising way contribute healing. By analyzing researches from last ten years, this review identifies potential benefits such compared traditional calcium-based approaches. Understanding impact on can have profound implications orthopedic and regenerative medicine. This evaluates efficacy through

Language: Английский

Citations

3
Characterization of anthracycline-induced cardiotoxicity by diffusion tensor magnetic resonance imaging DOI Creative Commons
David Lohr, Arne Thiele,

Max Stahnke

et al.

Basic Research in Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

Abstract Anthracyclines are highly potent anti-cancer drugs, but their clinical use is limited by severe cardiotoxic side effects. The impact of anthracycline-induced cardiotoxicity (AIC) on left ventricular (LV) microarchitecture and diffusion properties remains unknown. This study sought to characterize AIC cardiovascular magnetic resonance tensor imaging (DTI). Mice were treated with Doxorubicin (DOX; n = 16) for induction or saline as corresponding control ( 15). Cardiac function was assessed via echocardiography at the end period. Whole hearts 8 per group) scanned ex vivo high-resolution DTI 7 T. Results correlated histopathology mass spectrometry imaging. demonstrated systolic dysfunction (LVEF 52 ± 3% vs. 43 6%, P < 0.001), impaired global longitudinal strain (−19.6 2.0% −16.6 3.0%, 0.01), cardiac atrophy (LV index [mg/mm], 4.3 0.1 3.6 0.2, 0.01). Regional sheetlet angles significantly lower in AIC, whereas helix angle relative helicity remained unchanged. In fractional anisotropy increased (0.12 0.01 0.14 0.02, 0.05). DOX-treated mice displayed higher planar less spherical C Planar 0.07 0.09 0.01, 0.01; Spherical 0.89 0.87 yielded good discriminatory power distinguish between without (c-index 0.91 0.84, respectively, both associated regional changes no major abnormalities LV microarchitecture. geometric shape altered AIC. may provide a new tool myocardial characterization patients which warrants future studies evaluate its diagnostic utility.

Language: Английский

Citations

2
Cellular Scale Curvature in Bioceramic Scaffolds Enhanced Bone Regeneration by Regulating Skeletal Stem Cells and Vascularization DOI
Yang Liu, Yue Wang,

Minmin Lin

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(29)

Published: June 24, 2024

Critical-sized segmental bone defects cannot heal spontaneously, leading to disability and significant increase in mortality. However, current treatments utilizing grafts face a variety of challenges from donor availability poor osseointegration. Drugs such as growth factors cancer risk are very costly. Here, porous bioceramic scaffold that promotes regeneration via solely mechanobiological design is reported. Two types scaffolds with high versus low pore curvatures created using high-precision 3D printing technology fabricate radius the 100s micrometers. While both able support formation, high-curvature pores induce higher ectopic formation increased vessel invasion. Scaffolds also promote faster critical-sized by activating mechanosensitive pathways. High-curvature recruits skeletal stem cells type H vessels periosteum marrow during early phase repair. have survival transplanted GFP-labeled (SSCs) recruit more host SSCs. Taken together, defined micrometer-scale demonstrate approach for orthopedic design.

Language: Английский

Citations

2
Self-assembled peptide hydrogel loaded with functional peptide Dentonin accelerates vascularized bone tissue regeneration in critical-size bone defects DOI Creative Commons
Yijuan Liu, Li Li, Mengjiao He

et al.

Regenerative Biomaterials, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 1, 2024

Abstract Regeneration of oral craniofacial bone defects is a complex process, and reconstruction large without the use exogenous cells or bioactive substances remains major challenge. Hydrogels are highly hydrophilic polymer networks with potential to promote tissue regeneration. In this study, functional peptide Dentonin was loaded onto self-assembled hydrogels (RAD) constitute functionally self-assembling RAD/Dentonin hydrogel scaffolds view that could facilitate vascularized regeneration in critical-size calvarial defects. The functionalized forms ordered β-sheet supramolecular structures via non-covalent interactions like hydrogen bonding, ultimately assembling into nano-fiber network. exhibited desirable porosity swelling properties, appropriate biodegradability. supported adhesion, proliferation three-dimensional migration marrow mesenchymal stem (BMSCs) has induce differentiation BMSCs towards osteogenesis through activation Wnt/β-catenin pathway. Moreover, modulated paracrine secretion increased migration, tube formation angiogenic gene expression human umbilical vein endothelial (HUVECs), which boosted capacity HUVECs. vivo, significantly strengthened rat defect. Taken together, these results indicated effectively enhance osteogenic BMSCs, indirectly effects HUVECs, vivo. Thus, it promising material for maxillofacial

Language: Английский

Citations

2
Revolutionizing bone defect healing: the power of mesenchymal stem cells as seeds DOI Creative Commons

Yueyao Zhang,

Mengke Fan, Yingze Zhang

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 21, 2024

Bone defects can arise from trauma or pathological factors, resulting in compromised bone integrity and the loss absence of tissue. As we are all aware, repairing is a core problem tissue engineering. While minor self-repair if periosteum remains intact normal osteogenesis occurs, significant conditions such as congenital imperfecta present substantial challenges to self-healing. research on mesenchymal stem cell (MSC) advances, new fields application have emerged; however, their orthopedics one most established clinically valuable directions. This review aims provide comprehensive overview progress regarding MSCs treatment diverse defects. MSCs, multipotent cells, offer advantages due immunomodulatory properties ability undergo osteogenic differentiation. The will encompass characteristics within microenvironment summarize different types defects, ranging fundamental animal studies clinical applications.

Language: Английский

Citations

2
Advanced therapies in orthopaedics DOI Creative Commons
Tobias Winkler, Sven Geißler, Tazio Maleitzke

et al.

EFORT Open Reviews, Journal Year: 2024, Volume and Issue: 9(9), P. 837 - 844

Published: Sept. 1, 2024

Advanced therapies are expected to play a crucial role in supporting repair after injury, halting the degeneration of musculoskeletal tissue enable and promote physical activity. Despite advancements, progress developing advanced orthopaedics lags behind specialties like oncology, since innovative regenerative treatment strategies fall short their expectations clinical trials. Researchers should focus on understanding mechanism action investigated target before conducting Strategic research networks needed that not only enhance scientific exchange among like-minded researchers but need include early commercial views, companies venture perspectives, regulatory insights reimbursement perspectives. Only such collaborations essential roadblocks towards trials go-to-patients be overcome.

Language: Английский

Citations

1
Bone marrow from periacetabular osteotomies as a novel source for human mesenchymal stromal cells DOI Creative Commons

Maximilian Handke,

Anastasia Rakow, Debora Singer

et al.

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 3, 2023

Abstract Background Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are used in regenerative medicine and related research involving immunomodulatory, anti-inflammatory, anti-fibrotic functions. Isolation of BM-MSCs from samples obtained during total hip arthroplasty (THA) is routinely possible. Advanced age comorbidities the majority patients undergoing THA limit their applicability. Our study aimed to evaluate potential bone marrow periacetabular osteotomy (PAO) as a novel source young donors by analyzing cell yield characteristics. Methods were anterior Os ilium or superior pubis PAO femoral cavity primary THA. mononuclear (BM-MNCs) was performed density gradient centrifugation. The compared terms BM-MSC yield, colony formation proportion within BM-MNC population using flow cytometry analysis. characterized based on expression BM-MSC-specific surface markers. functionality quantifying post-thaw viability, metabolic activity, proliferation capacity, senescence-associated beta galactosidase (SA-β-gal) expression, trilineage differentiation major secretome proteins. Results BM-MNCs possible reliable reproducible manner when containing more than 0.24 g marrow. younger group. contained less led lower number after first culture passage higher capacity. This results two, normalized sample weight. showed increased secretion TGF-β1, TIMP2, VEGF upon osteogenic differentiation. revealed similar regarding onset SA-β-gal Conclusions We suggest that promising for donors. Limited absolute due low weight must be considered early passages might critical range clinical applications this source. capacity growth factor may beneficial future therapies, vitro models, tissue engineering.

Language: Английский

Citations

2
Exploration of Key Regulatory Factors for Continuous Regulation of Osteogenic Differentiation in Mesenchymal Stem Cells Based on Transcriptomic Sequencing DOI Creative Commons
Tao Liu, Yu Pan, Linfeng Li

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 12, 2024

Abstract In this study, we conducted an integrated analysis of high-throughput transcriptomic sequencing data to identify and validate the biological molecules that dynamically regulate osteogenic differentiation Mesenchymal Stem Cells (MSCs). Through analysis, taking into account expression levels genes in human tissues experimental validation, identified PTBP1, H2AFZ, TTPAL (C20ORF121) as pivotal regulators govern fate MSC differentiation. This article represents first utilization transcriptomics for identifying regulatory factors involved osteogenesis. study holds significant importance investigating crucial determine differentiation, with notable clinical implications. approach will lead a better understanding complex processes molecular mechanisms underlying diseases.

Language: Английский

Citations

0
Research progress of gene therapy combined with tissue engineering to promote bone regeneration DOI Creative Commons
Xiangyu Chu, Yuan Xiong, Li Lu

et al.

APL Bioengineering, Journal Year: 2024, Volume and Issue: 8(3)

Published: Sept. 1, 2024

Gene therapy has emerged as a highly promising strategy for the clinical treatment of large segmental bone defects and non-union fractures, which is common need. Meanwhile, many preclinical data have demonstrated that gene cell therapies combined with optimal scaffold biomaterials could be used to solve these tough issues. Bone tissue engineering, an interdisciplinary field combining cells, biomaterials, molecules stimulatory capability, provides alternatives enhance regeneration. To deliver localize growth factors associated intracellular signaling components into defect site, strategies bioengineering achieve uniform distribution sustained release ensure mesenchymal stem osteogenesis. In this review, we will describe process molecular changes during normal fracture healing, followed by advantages disadvantages various vectors engineering. The other bioactive peptides in regeneration particularly discussed. Finally, gene-activated illustrated through description characteristics synthetic methods.

Language: Английский

Citations

0