Engineered myeloid precursors differentiate into osteoclasts and resorb heterotopic ossification in mice DOI Creative Commons

Cameron Rementer,

Apichai Yavirach, Worakanya Buranaphatthana

et al.

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

Published: Nov. 22, 2024

Introduction Heterotopic ossification (HO) occurs following orthopedic trauma, spinal cord injuries, brain trauma and limb amputations. Once symptomatic, HO causes pain, limited mobility decreased quality of life. Current treatments are have significant complications with high recurrence rates, underscoring the need for improved therapeutic interventions. Osteoclasts (OCs) physiological bone resorptive cells that secrete enzymes protons to degrade bone. Methods In this study, we describe use genetically engineered OCs as a novel cell therapy approach treat HO. Inducible, myeloid precursors (iRANK cells) treated chemical inducer dimerization (CID) differentiated into TRAP + multinucleated resorbed mineralized tissues in vitro . Results vivo , BMP-2-induced murine lesions were significantly regressed treatment using iRANK concomitant systemic administration CID. Moreover, many MMP9 GFP indicating they from delivered cells. Discussion summary, these data con rm ability differentiate resorb paving way OC delivery promising treatment.

Language: Английский

Multifunctional Injectable Bioadhesive with Toll-like Receptor 4 and Myeloid Differentiation Factor 2 Antagonistic Anti-inflammatory Potential for Periodontal Regeneration DOI Creative Commons

Shuting Gao,

Huihua Li, Zekun Li

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Effectively addressing inflammation in periodontitis is challenging as conventional injectable hydrogels typically require the addition of drugs to provide sufficient anti-inflammatory effects. To overcome this limitation, we developed a multifunctional hydrogel with inherent properties that antagonize Toll-like receptor 4 and myeloid differentiation factor 2 complex (TLR4-MD2). This allows for direct inhibition inflammatory pathways without need additional drugs. We identified xylitol, caffeic acid, citric acid natural materials effectively meet biological needs antibacterial effects well support bone regeneration. With mind, caffeic-acid-modified poly(xylitol succinate) (PXS)-based iCPC@MgO composite tested its potential application periodontal The demonstrated rapid wet tissue adhesion injectability, which are ascribed incorporating catechol groups derived from acid. Intriguingly, PXS polymer used synthesizing was found possess act an antagonist TLR4-MD2 complex. also exhibited outstanding efficiency against Porphyromonas gingivalis Aggregatibacter actinomycetemcomitans by stimulating antibiotic synthesis within bacteria disrupting bacterial cell walls. In mouse model, therapeutic reducing factors, inhibiting dominant periodontitis-associated bacteria, maintaining subgingival microbiota balance regenerative These properties, combined their ecofriendly nature, firmly established highly promising option use therapy healing, repair, regeneration various other conditions.

Language: Английский

Citations

0

Chronic heavy alcohol consumption impairs the ability of demineralized allogenic bone matrix to support osteoinduction in alcohol-naïve rats DOI Creative Commons
Russell T. Turner, Amida Kuah,

Cynthia H Trevisiol

et al.

Bone Reports, Journal Year: 2025, Volume and Issue: 25, P. 101836 - 101836

Published: March 12, 2025

Allografts play an important role in treatment of complex bone fractures and deformities. The purpose this study was to test the hypothesis that alcohol consumption impairs graft incorporation healing by two mechanisms: (1) lowering osteoinductive capacity (2) suppressing formation. We performed experiments using a demineralized allogeneic matrix (DBM) model which DBM harvested from donor rats fed control or ethanol diet implanted subcutaneously into recipient diet. also evaluated efficacy intermittent parathyroid hormone (PTH) on (DBM diet) critical size defect model. Bone formed during osteoinduction measured micro-computed tomography. Experiment 1: volume lower ethanol-consuming donors 6 weeks following implantation recipients diet, indicating exposure lowered capacity. 2: 3 compared recipients. 3: Ethanol resulted tendency for (p = 0.085) whereas PTH higher Our results suggest chronic heavy allograft may impair negative outcome be worsened intake healing. Additionally, has potential increase both abstinent alcohol-consuming donors.

Language: Английский

Citations

0

Study on the Pathological Mechanisms and Impact of Osteoporotic Fractures under the Influence of Aging DOI

熔 刘

Aging Research, Journal Year: 2025, Volume and Issue: 12(03), P. 217 - 222

Published: Jan. 1, 2025

Language: Английский

Citations

0

Macrophage ATF6 accelerates corticotomy-assisted orthodontic tooth movement through promoting Tnfα transcription DOI Creative Commons

Zhichun Jin,

Hao Xu,

Weiye Zhao

et al.

International Journal of Oral Science, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 1, 2025

Abstract Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon (RAP). Despite its therapeutic effects, surgical risk and unclear mechanism hamper application. Numerous evidences support macrophages as key immune cells during bone remodeling. Our study discovered that monocyte-derived primarily exhibited pro-inflammatory phenotype dominated remodeling in corticotomy CX3CR1 CreERT2 ; R26 GFP lineage tracing system. Fluorescence staining, flow cytometry analysis, western blot determined significantly enhanced expression of binding immunoglobulin protein (BiP) emphasized activation sensor activating transcription factor 6 (ATF6) macrophages. Then, we verified macrophage specific ATF6 deletion (ATF6 f/f mice) decreased proportion therefore blocked acceleration effect corticotomy. In contrast, overexpression exaggerated movement. vitro experiments also proved higher was positively correlated with ATF6. At level, RNA-seq CUT&Tag analysis demonstrated modulated macrophage-orchestrated inflammation through interacting Tnfα promotor augmenting transcription. Additionally, molecular docking simulation dual-luciferase reporter system indicated possible sites outside traditional endoplasmic reticulum-stress response element (ERSE). Taken together, may aggravate promoting macrophages, suggesting represent promising target for non-invasive accelerated orthodontics.

Language: Английский

Citations

0

Essential role of RANK-NF-κB signaling pathway in spinal deformities: Insights from largemouth bass and zebrafish models DOI
Li Zhuang,

Yajing Ouyang,

Xiaoyi Yuan

et al.

Aquaculture, Journal Year: 2025, Volume and Issue: unknown, P. 742570 - 742570

Published: April 1, 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

Enhanced functionalities of biomaterials through metal ion surface modification DOI Creative Commons
Yujie Tao, Wayne Nishio Ayre, Liming Jiang

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: April 14, 2025

The development of new artificial biomaterials for bone defect repair is an ongoing area clinical research. Metal ions such as zinc, copper, magnesium, calcium, strontium, silver, and cerium play various roles in tissue regeneration the human body possess a range biochemical functions. Studies have demonstrated that appropriate concentrations these metal can promote osteogenesis angiogenesis, inhibit osteoclast activity, deter bacterial infections. Researchers incorporated into using methods to create materials with enhanced osteogenic antibacterial capabilities. In addition properties all aforementioned ions, Zn, Sr, Ce indirectly by inhibiting activity. Cu, Mg, Sr significantly enhance while Ag, reduce likelihood infection inflammation caused implanted materials. This paper reviews mechanisms through which growth improve activity biomaterials. It also summarizes common loading on surface different metals highlights potential applications

Language: Английский

Citations

0

Brevilin A, a novel BNIP3 inhibitor suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss via impairing mitophagy and mitochondrial metabolism DOI
Rui Zhou, Yiyuan Wang, Siyi Liu

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: 143, P. 156774 - 156774

Published: May 1, 2025

Language: Английский

Citations

0

Osteoclasts drive bone formation in ectopic and orthotopic environments DOI Creative Commons
Yang Zhang,

Taozhao Yu,

Qianfeng Xiang

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 322, P. 123377 - 123377

Published: May 1, 2025

To date, cell-based approaches to stimulate bone formation have primarily focused on mesenchymal stromal cells (MSCs) for their supposed osteogenic potential, but despite some pre-clinical successes, clinical outcomes remained unsatisfactory. Emerging data suggest that osteoclasts play crucial roles in stimulating beyond catabolic function resorption. Interestingly, osteoclastic activity precedes osteoblastic the physiological remodeling cycle. explore role of further, we prepared osteoclast-based constructs and implanted them (i) ectopically evaluate potential induce formation, (ii) orthotopically effects regeneration. Remarkably, containing primary mouse showed consistent robust de novo which presented comparable efficacy BMP-2 treatment. Additionally, observed marrow upon ectopic implantation (incidence 73 %) loaded controls 91 %). Importantly, macrophages (MФs) or scaffold only (negative control) neither nor formation. Further, a cranial defect model confirmed stimulatory regeneration capabilities Osteoclast-based constructs, evidenced by 2.5-fold increased compared only. These findings demonstrate osteoinduction osteogenesis capacity osteoclasts, reshaping our understanding opening new avenues design development repair.

Language: Английский

Citations

0

High-fat diet-induced osteoporosis in mice under hypoxic conditions DOI Creative Commons
Yajun Qiao, Huimin Zheng, Ruiying Cheng

et al.

BMC Musculoskeletal Disorders, Journal Year: 2025, Volume and Issue: 26(1)

Published: May 16, 2025

Language: Английский

Citations

0