Dynamics of postnatal bone development and epiphyseal synostosis in the caprine autopod DOI Creative Commons
Christopher J. Panebianco,

Maha Essaidi,

Eugene H. Barnes

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 26, 2024

Abstract Bones develop to structurally balance strength and mobility. Bone developmental dynamics are influenced by whether an animal is ambulatory at birth ( i.e., precocial). Precocial species, such as goats, advanced skeletal maturity in utero, making them useful models for studying the of bone formation under mechanical load. Here, we used microcomputed tomography histology characterize postnatal development autopod caprine lower forelimb. The features two toes, fused metacarpal synostosis i.e. , fusion) prior birth. Our analysis focused on phalanges 1 (P1) metacarpals goat from through adulthood (3.5 years). P1 cortical densified rapidly after (half-life using one-phase exponential decay model (τ 1/2 = 1.6 ± 0.4 months), but thickness increased continually 7.2 2.7 mo). Upon normalization body mass, normalized polar moment inertia was constant over time, suggestive structural load adaptation. trabecular number 6.7 2.8 mo) 6.6 2.0 until maturity, while trabeculae grew primarily thickening 7.9 2.2 Unlike prenatal fusion diaphysis, epiphyses occurred postnatally, growth plate closure, a unique fibrocartilaginous endochondral ossification. These findings implicate loading precocial goats identify novel event epiphysis.

Язык: Английский

Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression DOI Creative Commons
Yi‐Cheng Zhu,

Jiaoshun Chen,

Chen Chen

и другие.

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 23, 2025

The tumor microenvironment functions as a dynamic and intricate ecosystem, comprising diverse array of cellular non-cellular components that precisely orchestrate pivotal behaviors, including invasion, metastasis, drug resistance. While unraveling the interplay between behaviors represents tremendous challenge, recent research illuminates crucial biological phenomenon known mechanotransduction. Within microenvironment, mechanical cues like tensile stress, shear stiffness play role by activating mechanosensitive effectors such PIEZO proteins, integrins, Yes-associated protein. This activation initiates cascades intrinsic signaling pathways, effectively linking physical properties tissues to their physiological pathophysiological processes morphogenesis, regeneration, immunity. mechanistic insight offers novel perspective on how within impact behaviors. intricacies are yet be fully elucidated, it exhibits distinct attributes from non-malignant tissues, elevated solid stresses, interstitial hypertension, augmented matrix stiffness, enhanced viscoelasticity. These traits exert notable influences progression treatment responses, enriching our comprehension multifaceted nature microenvironment. Through this innovative review, we aim provide new lens decipher contexts, broadening knowledge these factors promote or inhibit thus offering valuable insights identify potential targets for anti-tumor strategies.

Язык: Английский

Процитировано

3
Estrogen and estrogen receptors mediate the mechanobiology of bone disease and repair DOI
Vivian Y. Shi, Elise F. Morgan

Bone, Год журнала: 2024, Номер 188, С. 117220 - 117220

Опубликована: Авг. 5, 2024

Язык: Английский

Процитировано

11
Cell enlargement modulated by GATA4 and YAP instructs the senescence-associated secretory phenotype DOI Creative Commons

J. P. W. Joung,

Y.‐A. Heo,

Yeonju Kim

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 17, 2025

Dynamic changes in cell size are associated with development and pathological conditions, including aging. Although enlargement is a prominent morphological feature of cellular senescence, its functional implications unknown; moreover, how senescent cells maintain their state less understood. Here we show that an extensive remodeling actin cytoskeleton necessary for establishing senescence-associated pro-inflammatory secretory phenotype (SASP). This attributed to balancing act between the SASP regulator GATA4 mechanosensor YAP on expression Rho family GTPase RHOU. Genetic or pharmacological interventions reduce attenuate minimal effect senescence growth arrest. Mechanistically, couples nuclear localization NF-κB via Linker Nucleoskeleton Cytoskeleton (LINC) complex. RhoU protein accumulates mouse adipose tissue under senescence-inducing conditions. Furthermore, RHOU correlates during human Thus, our study highlights unexpected instructive role modulating reveals mechanical branch regulatory network. Senescent accumulate aging exhibit enlargement, function which has been unclear decades. Here, authors identify antagonistic genetic circuit hypertrophy reveal SASP.

Язык: Английский

Процитировано

1
Skeletal stem and progenitor cells in bone physiology, ageing and disease DOI
Seppe Melis, Dana Trompet, Andrei S. Chagin

и другие.

Nature Reviews Endocrinology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 8, 2024

Язык: Английский

Процитировано

6
Inhibition of Mitochondrial Fission Reverses Simulated Microgravity-induced Osteoblast Dysfunction by Enhancing Mechanotransduction and Epigenetic Modification DOI Creative Commons
Qiusheng Shi, Yaxin Song,

Jingqi Cao

и другие.

Research, Год журнала: 2025, Номер 8

Опубликована: Янв. 1, 2025

Simulated microgravity (SMG) poses substantial challenges to astronaut health, particularly impacting osteoblast function and leading disuse osteoporosis. This study investigates the adverse effects of SMG on osteoblasts, focusing changes in mitochondrial dynamics their consequent cellular energy metabolism mechanotransduction pathways. We discovered that markedly reduced expression differentiation markers promoted fission, as indicated by an increase punctate mitochondria, a decrease length, reduction cristae density. These alterations are linked elevated reactive oxygen species levels, ΔΨm, metabolic shift from oxidative phosphorylation glycolysis, resulting decreased adenosine triphosphate production, which all indicative dysfunction. Our results showed treatment with division inhibitor-1 (mdivi-1), fission inhibitor, effectively inhibited these SMG-induced effects, thereby maintaining structure promoting differentiation. Furthermore, disrupted critical processes, affecting paxillin expression, RhoA–ROCK–Myosin II pathway, actin dynamics, subsequently altered nuclear morphology Yes-associated protein signaling. Notably, mdivi-1 prevented disruptions Moreover, our chromatin remodeling histone methylation, epigenetic barriers osteogenic differentiation, can be reversed targeting further highlighting significance environment. Therefore, emerges promising therapeutic strategy alleviate dysfunction under conditions, providing novel approaches maintain bone health during prolonged space missions safeguard well-being.

Язык: Английский

Процитировано

0
The physiological and pathogenic roles of yes-associated protein/transcriptional co-activator with PDZ-binding motif in bone or skeletal motor system-related cells DOI Open Access
Yao Huang, Xueqian Ouyang, Jinghua Tan

и другие.

CytoJournal, Год журнала: 2025, Номер 22, С. 13 - 13

Опубликована: Фев. 8, 2025

Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are the primary downstream effectors of Hippo signaling pathway. This pathway plays a crucial role in regulating organ size, maintaining tissue homeostasis, controlling cellular processes such as fate determination development. review provides an overview current understanding how regulators YAP TAZ contribute to physiological pathological tissues cells associated skeletal motor system. The underlying molecular mechanisms mechanical transduction were reviewed.

Язык: Английский

Процитировано

0
From passive bionics to active adaptation: a new strategy for tissue regeneration based on cell-autonomous construction of microenvironments DOI Creative Commons

Ji-ji Zhou,

Zhenyu Wen, Zhikai Wang

и другие.

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
CYR61 delivery promotes angiogenesis during bone fracture repair DOI Creative Commons
Annemarie Lang,

Emily A. Eastburn,

Mousa Younesi

и другие.

npj Regenerative Medicine, Год журнала: 2025, Номер 10(1)

Опубликована: Апрель 22, 2025

Abstract Compromised vascular supply and insufficient neovascularization impede bone repair, increasing risk of non-union. CYR61, Cysteine-rich angiogenic inducer 61kD (also known as CCN1), is a matricellular growth factor that has been implicated in fracture repair. Here, we map the distribution endogenous CYR61 during repair evaluate effects recombinant delivery on vascularized regeneration. In vitro, treatment did not alter chondrogenesis or osteogenic gene expression, but significantly enhanced angiogenesis. mouse femoral model, cartilage formation, accelerated Early initiation ambulatory mechanical loading disrupted CYR61-induced neovascularization. Together, these data indicate can enhance angiogenesis particularly for fractures with stable fixation, may have therapeutic potential limited blood vessel supply.

Язык: Английский

Процитировано

0
Metabolite-dependent m6A methylation driven by mechanotransduction-metabolism-epitranscriptomics axis promotes bone development and regeneration DOI Creative Commons
Zhuo Li,

Zhengnan Guo,

Zhengmeng Yang

и другие.

Cell Reports, Год журнала: 2025, Номер 44(5), С. 115611 - 115611

Опубликована: Апрель 23, 2025

Язык: Английский

Процитировано

0
Cell Ratio-Dependent Osteoblast–Endothelial Cell Crosstalk Promoting Osteogenesis–Angiogenesis Coupling via Regulation of Microfluidic Perfusion and Paracrine Signaling DOI Creative Commons
Yuexin Wang, Shu Chen, Wenwen Fan

и другие.

Micromachines, Год журнала: 2025, Номер 16(5), С. 539 - 539

Опубликована: Апрель 30, 2025

Osteogenesis–angiogenesis coupling, a dynamic and coordinated interaction between skeletal vascular cells, is essential for fracture healing. However, the effects of these cell ratios their interactions under microfluidic perfusion paracrine signaling on osteogenesis–angiogenesis coupling have rarely been reported. In this study, static models were developed osteogenic angiogenic two compared. Static co-cultures MC3T3-E1 bEnd.3 cells in Transwell inserts showed ratio-dependent reciprocal relation: ratio 1:1 (MC3T3-E1:bEnd.3) favored osteogenesis, whereas 2:1 promoted angiogenesis. On that basis, we an chip based technology. The within further enhanced mineralizing effect osteoblasts endothelial respectively, increased secretion growth factor (VEGF) bone morphogenetic protein-2 (BMP-2) compared to insert model. results suggest potential mediated by signaling. Overall, not only powerful model understanding bone–vascular but also scalable platform high-throughput drug screening personalized therapy development fractures.

Язык: Английский

Процитировано

0