Mechanical regulation of bone remodeling

Bone Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: Feb. 18, 2022

Abstract Bone remodeling is a lifelong process that gives rise to mature, dynamic bone structure via balance between formation by osteoblasts and resorption osteoclasts. These opposite processes allow the accommodation of bones mechanical forces, altering mass in response changing conditions. Mechanical forces are indispensable for homeostasis; skeletal formation, resorption, adaptation dependent on signals, loss stimulation can therefore significantly weaken structure, causing disuse osteoporosis increasing risk fracture. The exact mechanisms which body senses transduces regulate have long been an active area study among researchers clinicians. Such research will lead deeper understanding disorders identify new strategies rejuvenation. Here, we discuss properties, mechanosensitive cell populations, mechanotransducive signaling pathways system.

Language: Английский

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Mechanics of 3D Cell–Hydrogel Interactions: Experiments, Models, and Mechanisms

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(18), P. 11085 - 11148

Published: Sept. 2, 2021

Hydrogels are highly water-swollen molecular networks that ideal platforms to create tissue mimetics owing their vast and tunable properties. As such, hydrogels promising cell-delivery vehicles for applications in engineering have also emerged as an important base ex vivo models study healthy pathophysiological events a carefully controlled three-dimensional environment. Cells readily encapsulated resulting plethora of biochemical mechanical communication mechanisms, which recapitulates the natural cell extracellular matrix interaction tissues. These interactions complex, with multiple invariably coupled spanning length time scales. To identify underlying mechanisms involved, integrated experimental computational approach is ideally needed. This review discusses state our knowledge on cell–hydrogel interactions, focus mechanics transport, this context, highlights recent advancements experiments, mathematical modeling. The begins background thermodynamics physics fundamentals govern hydrogel transport. focuses two main classes hydrogels, described semiflexible polymer represent physically cross-linked fibrous flexible representing chemically synthetic hydrogels. In review, we highlight five involve key cellular functions related communication, mechanosensing, migration, growth, deposition elaboration. For each these functions, experiments most up date modeling strategies discussed then followed by summary how tune properties achieve desired functional outcome. We conclude linking make case need integrate advance fundamental understanding cell–matrix will ultimately help new therapeutic approaches enable successful engineering.

Language: Английский

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Biomaterial-induced pathway modulation for bone regeneration

Biomaterials, Journal Year: 2022, Volume and Issue: 283, P. 121431 - 121431

Published: Feb. 18, 2022

Embryogenic developmental processes involve a tightly controlled regulation between mechanical forces and biochemical cues such as growth factors, matrix proteins, cytokines. This interplay remains essential in the mature body, with aberrant pathway signaling leading to abnormalities atherosclerosis cardiovascular system, inflammation tendon tissue, or osteoporosis bone. The aim of bone regenerative strategies is develop tools procedures that will harness body's own self-repair ability order successfully regenerate even very large complex defects restore normal function. To achieve this, understanding pathways govern progenitor differentiation towards osteogenic lineages, their phenotypical maintenance, construction functional tissue imperative subsequently therapies mimic these processes. While body literature exists describes how stimuli guide cell behavior culture dish, due lack an appropriate environment, signals are often insufficient inappropriate for achieving desirable response body. Moreover, rarely rely on stimulus, factor alone, instead comprise carrier biomaterial introduces different microenvironment from dish. Therefore, this review, we discuss which biomaterials elicit influence relevant regeneration describe mechanisms behind effects, inspire development novel, more effective therapies.

Language: Английский

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Trends in mechanobiology guided tissue engineering and tools to study cell-substrate interactions: a brief review

Biomaterials Research, Journal Year: 2023, Volume and Issue: 27(1)

Published: Feb. 9, 2023

Sensing the mechanical properties of substrates or matrix by cells and tissues, subsequent downstream responses at cellular, nuclear epigenetic levels outcomes are beginning to get unraveled more recently. There have been various instances where researchers established underlying connection between cellular mechanosignalling pathways physiology, differentiation, also tissue pathology. It has now accepted that mechanosignalling, alone in combination with classical pathways, could play a significant role fate determination, development, organization tissues. Furthermore, as mechanobiology is gaining traction, so do techniques ponder gain insights into still pathways. This review would briefly discuss some interesting works wherein it shown specific alteration lead determination stem differentiated such osteoblasts, adipocytes, tenocytes, cardiomyocytes, neurons, how these being utilized for development organoids. cover developed employed explore effects including imaging mechanosensing proteins, atomic force microscopy (AFM), quartz crystal microbalance dissipation measurements (QCMD), traction (TFM), microdevice arrays, Spatio-temporal image analysis, optical tweezer measurements, mechanoscanning ion conductance (mSICM), acoustofluidic interferometric device (AID) forth. provide who work on exploiting control functions engineering regenerative applications, will shed light advancements be unravel unknown field mechanobiology.

Language: Английский

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Discoidin domain receptor 2 is an important modulator of BMP signaling during heterotopic bone formation

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

Published: Jan. 2, 2025

Abstract Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification (HO). Understanding accessory factors modulating BMP signaling would provide both a means of enhancing BMP-dependent regeneration while preventing HO. This study focuses on the ability collagen receptor, discoidin domain receptor 2 (DDR2), to regulate activity. As will be shown, induction formation by subcutaneous BMP2 implants is severely compromised in Ddr2 -deficient mice. In addition, deficiency attenuates HO mice expressing ACVR1 mutation associated with human fibrodysplasia ossificans progressiva. cells migrating into implants, DDR2 co-expressed GLI1, skeletal stem cell marker, and DDR2/GLI1-positive participate BMP2-induced where they contribute chondrogenic osteogenic lineages. Consistent this distribution, conditional knockout Gli1- inhibited same extent seen globally animals. response was explained selective inhibition Gli1 + proliferation without changes apoptosis. The basis requirement explored further using marrow stromal cells. Although BMP2-dependent chondrocyte osteoblast differentiation vivo, formation, early responses including SMAD phosphorylation remained largely intact. Instead, reduced nuclear/cytoplasmic ratio Hippo pathway intermediates, YAP TAZ. suggests that regulates pathway-mediated matrix, which subsequently affect responsiveness. summary, an important modulator potential therapeutic target treating

Language: Английский

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BMP6/TAZ-Hippo signaling modulates angiogenesis and endothelial cell response to VEGF

Angiogenesis, Journal Year: 2020, Volume and Issue: 24(1), P. 129 - 144

Published: Oct. 6, 2020

Abstract The BMP/TGFβ-Smad, Notch and VEGF signaling guides formation of endothelial tip stalk cells. However, the crosstalk bone morphogenetic proteins (BMPs) vascular growth factor receptor 2 (VEGFR2) has remained largely unknown. We demonstrate that BMP family members regulate VEGFR2 signaling, act via TAZ-Hippo pathway. BMPs were found to be regulated after gene transfer in C57/Bl6 mice a porcine myocardial ischemia model. 2/4/6 identified as endothelium-specific targets VEGF. BMP2 modulated VEGF-mediated sprouting Delta like Canonical Ligand 4 (DLL4). BMP6 by regulating expression acted Hippo effector TAZ, known cell survival/proliferation, dysregulated cancer. In matrigel plug assay nude was further demonstrated induce angiogenesis. is first member directly both neovessel formation. It may thus serve target pro/anti-angiogenic therapies.

Language: Английский

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A review of biomimetic scaffolds for bone regeneration: Toward a cell‐free strategy

Bioengineering & Translational Medicine, Journal Year: 2020, Volume and Issue: 6(2)

Published: Dec. 2, 2020

In clinical terms, bone grafting currently involves the application of autogenous, allogeneic, or xenogeneic grafts, as well natural artificially synthesized materials, such polymers, bioceramics, and other composites. Many these are associated with limitations. The ideal scaffold for tissue engineering should provide mechanical support while promoting osteogenesis, osteoconduction, even osteoinduction. There various structural complications difficulties to be considered. Here, we describe biomimetic possibilities modification synthetic materials through physical chemical design facilitate repair. This review summarizes recent progresses in strategies constructing scaffolds, including ion-functionalized decellularized extracellular matrix micro- nano-scale structures, reactive scaffolds induced by factors, acellular scaffolds. fabrication techniques along current repair, described. developments each category discussed terms connection between interactions endogenous cells. As advances move toward setting, demonstration therapeutic efficacy novel designs is critical.

Language: Английский

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BMP‐2 Signaling and Mechanotransduction Synergize to Drive Osteogenic Differentiation via YAP/TAZ

Advanced Science, Journal Year: 2020, Volume and Issue: 7(15)

Published: June 16, 2020

Abstract Growth factors and mechanical cues synergistically affect cellular functions, triggering a variety of signaling pathways. The molecular levels such cooperative interactions are not fully understood. Due to its role in osteogenesis, the growth factor bone morphogenetic protein 2 (BMP‐2) is tremendous interest for regenerative medicine, osteoporosis therapeutics, beyond. Here, contribution BMP‐2 extracellular osteogenic commitment C2C12 cells investigated. It revealed that these two distinct pathways integrated at transcriptional level provide multifactorial control cell differentiation. activation genes requires cooperation pathway‐associated Smad1/5/8 heteromeric complexes mechanosensitive YAP/TAZ translocation. further demonstrated Smad remain bound onto active on target genes, even after removal, suggesting they act as “molecular memory unit.” Thus, synergistic stimulation with drives differentiation programmable fashion.

Language: Английский

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The Development of Molecular Biology of Osteoporosis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(15), P. 8182 - 8182

Published: July 30, 2021

Osteoporosis is one of the major bone disorders that affects both women and men, causes deterioration strength. Bone remodeling maintains mass mineral homeostasis through balanced action osteoblasts osteoclasts, which are responsible for formation resorption, respectively. The imbalance in known to be main cause osteoporosis. can result various molecules produced by cell acts on other cells influence activity. understanding effect these help identify new targets therapeutics prevent treat disorders. In this article, we have focused osteoblasts, osteocytes, osteoclasts their mechanism cells. We also summarized different pharmacological osteoporosis treatments target molecular aspects minimize

Language: Английский

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Mechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Oct. 28, 2021

Abstract Mesenchymal stem cells adopt differentiation pathways based upon cumulative effects of mechanosensing. A cell’s mechanical microenvironment changes substantially over the course development, beginning from early stages in which are typically surrounded by other and continuing through later extracellular matrix. How erase memory some these microenvironments while locking others is unknown. Here, we develop a material culture system for modifying measuring degree to retain Using this system, discover that RGD adhesive motif fibronectin (representative matrix), known impart what often termed “mechanical memory” mesenchymal via nuclear YAP localization, erased HAVDI N-cadherin cell-cell contacts). These can be explained motor clutch model relates cellular traction force, deformation, resulting re-localization. Results demonstrate controlled storage removal proteins associated with possible defined programmable systems.

Language: Английский

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