Mechanobiology in Medicine最新文献

{"title":"Intraoperative mechanical characterization of vertebral bone quality during percutaneous kyphoplasty","authors":"Yudong Zhao,&nbsp;Sheng Lu,&nbsp;Pan Liu,&nbsp;Xufeng Bai,&nbsp;Zuoqi Zhang,&nbsp;Xiaobin Zhu,&nbsp;Shaobo Zhu","doi":"10.1016/j.mbm.2026.100211","DOIUrl":"10.1016/j.mbm.2026.100211","url":null,"abstract":"<div><div>Osteoporosis (OP) compromises bone strength and markedly increases the risk of vertebral compression fractures (VCFs), which are commonly treated with percutaneous kyphoplasty (PKP). Although bone mineral density (BMD) is widely used to diagnose OP and inform surgical planning, it primarily reflects bone mass rather than mechanical competence. Here, we propose an intraoperative method that derives a bulk-modulus-like mechanical index, <em>κ</em>, from the balloon pressure–volume response during PKP. This method enables direct mechanical assessment of vertebral bone quality without additional surgical trauma or procedural steps. To evaluate its feasibility and robustness, a three-dimensional lumbar vertebral model was reconstructed from computed tomography data, and finite element simulations were performed to characterize the relationship between <em>κ</em> and the elastic modulus of cancellous bone. The effects of balloon geometry, puncture trajectory, material anisotropy and heterogeneity, elastoplasticity, and cortical bone failure were also investigated. The results showed that <em>κ</em> decreased linearly with reductions in cancellous-bone elastic modulus, enabling clear differentiation among the simulated bone-health states. Variations in balloon geometry and puncture trajectory altered <em>κ</em> by less than 5.5%, indicating that the measurement is robust to clinically relevant procedural variations. Moreover, the linear relationship between <em>κ</em> and cancellous-bone modulus was preserved across increasingly realistic constitutive models. These findings establish a mechanically grounded framework for intraoperative assessment of vertebral bone quality and support the potential use of <em>κ</em> to inform PKP procedures, postoperative management, and the acquisition of patient-specific in vivo bone mechanical-property data.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"4 3","pages":"Article 100211"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148953256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of novel mechanosensitive ion channel TMEM63A impairs osteogenic differentiation and proliferation via disruption of cellular mechanotransduction","authors":"Meghana Davuluri,&nbsp;Rekha Sathian,&nbsp;Anna R. Cho,&nbsp;Ramana V. Davuluri,&nbsp;Yi-Xian Qin","doi":"10.1016/j.mbm.2026.100212","DOIUrl":"10.1016/j.mbm.2026.100212","url":null,"abstract":"<div><div>Skeletal homeostasis depends critically on the local mechanobiological microenvironment. While well-known mechanosensitive ion channels like Piezo1 and Piezo2 translate physical forces into immediate membrane ion fluxes, the proximal sensors regulating medium- and long-term osteogenic pathways remain poorly understood. Low-intensity pulsed ultrasound (LIPUS) is widely used clinically to accelerate fresh fracture repair, yet its underlying upstream mechanotransduction machinery is not fully characterized. Here, we identify TMEM63A – a stretch-activated cation channel – as a crucial mechanosensor required for mechanical stimuli-driven osteogenic differentiation and anabolic signaling for sustained response to the force. Thus, the <strong>objective of this study was to elucidate the function of TMEM63A in driving osteogenic differentiation and modulating ultrasound-driven anabolic signaling during mechanotransduction with both short- and long-term effects</strong>. In MC3T3-E1 pre-osteoblasts, stable shRNA-mediated knockdown (KD) of TMEM63A (∼63% mRNA and ∼60% protein reduction) significantly impaired osteogenic capacity. KD cells exhibited reduced alkaline phosphatase activity at Days 7 and 14, suppressed proliferation, attenuated early marker expression (Runx2, Alp, and Col1a1), and a marked reduction of LIPUS-evoked Ca²⁺ oscillations and nuclear β-catenin translocation. Genome-wide RNA sequencing revealed coordinated downregulation of bone formation, mineralization, and ossification networks in KD cells across Days 7 and 14. Gene set enrichment analysis (GSEA) demonstrated negative enrichment for Hallmark Wnt/<span><math><mrow><mi>β</mi></mrow></math></span>-catenin and PI3K-AKT-mTOR signaling pathways at Day 14, paired with positive enrichment for matrix-degradation and remodeling programs, consistent with <em>Mmp13</em> upregulation. Crucially, LIPUS treatment failed to rescue or engage these osteogenic programs in TMEM63A-deficient cells. Under Day 14 LIPUS, knockdown cells maintained negative enrichment of Hallmark Wnt/β-catenin signaling and Reactome Axin degradation, a positive readout of canonical Wnt activation, indicating that the β-catenin destruction complex remains active and continues to target β-catenin for degradation. Taken together, these findings establish TMEM63A as an essential mechanosensor that couples acoustic force stimulation via LIPUS to a Ca²⁺ → AKT → GSK3 β → β-catenin signaling axis to drive osteogenic transcription and bone formation through cellular mechanotransduction.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"4 3","pages":"Article 100212"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148995912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoring the lost heat of the joint: Thermomechanical stimulation as a candidate treatment for early-stage osteoarthritis","authors":"Antoine Reitzel,&nbsp;Deniz Cemre Turgut,&nbsp;Céline Samira Wyss,&nbsp;Vincent Stadelmann,&nbsp;Dominique P. Pioletti","doi":"10.1016/j.mbm.2026.100213","DOIUrl":"10.1016/j.mbm.2026.100213","url":null,"abstract":"<div><div>Two of the oldest osteoarthritis treatments, local heat and therapeutic exercise, have evolved along separate paths: heat as a symptomatic adjunct and exercise as a functional intervention. Neither intervention alone modifies the disease. This separation reflects clinical tradition, not joint physiology. Articular cartilage dissipates some of the energy absorbed during deformation. At rest, knee cartilage is 32–33 °C and warms toward 37 °C under loading, which enhances matrix production. Physical activity therefore provides two coupled cues: mechanical deformation and the resulting heat. These cues are successive stages of one physical event, not independent therapeutic levers. Critically, this coupling is impaired early in osteoarthritis. Under load, normal-appearing cartilage from an osteoarthritic joint dissipates roughly half as much energy as healthy cartilage. This deficit, which is undetectable by stiffness-based measures, prevents the tissue from heating itself to the optimal temperature range. In vitro, combined thermal and mechanical stimulation elicits stronger chondroinductive and chondroprotective responses than either cue alone, through pathways involving transient receptor potential vanilloid 4 (TRPV4) and TWIK-related potassium 1 (TREK1) channels, calcium signaling, and heat shock protein 70 (HSP70). We propose that early-stage osteoarthritis, when residual matrix and viable chondrocytes remain, offers a therapeutic window in which exogenous heat could restore the lost cue, potentially making exercise a structure-modifying intervention.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"4 3","pages":"Article 100213"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substrate pre-stretch reprograms macrophage behavior through surface topographical remodeling","authors":"Gang Yang ,&nbsp;Yi Han ,&nbsp;Tao Tang ,&nbsp;Yong-fu Xiong ,&nbsp;Jun-wei Wang ,&nbsp;Xiao-song Qing ,&nbsp;Chen Zhang","doi":"10.1016/j.mbm.2026.100194","DOIUrl":"10.1016/j.mbm.2026.100194","url":null,"abstract":"<div><div>Mechanical regulation of macrophages is increasingly recognized, but whether a mechanically preconditioned surface remains biologically instructive after loading has ceased is unclear. Here, we developed a custom uniaxial pre-stretch device to generate polydimethylsiloxane (PDMS) membranes with defined tensile histories and used this system to examine how substrate mechanical regulates macrophage behavior. Atomic force microscopy showed that pre-stretch reduced membrane step height and surface roughness without significantly changing elastic modulus or water contact angle, indicating selective remodeling of surface topography. RAW264.7 macrophages cultured on pre-stretched membranes exhibited increased cell and nuclear spreading, reduced roundness, and decreased F-actin intensity, accompanied by enhanced cell–substrate adhesion and increased migratory activity. Pre-stretched surfaces also promoted phagocytosis and reactive oxygen species generation without affecting proliferation. In addition, macrophages on pre-stretched membranes showed elevated expression of TNFα and IL-1β and increased TNF-α secretion, whereas Arg1 and IL-10 were not enhanced, indicating a shift toward a pro-inflammatory phenotype. These findings demonstrate that pre-stretched PDMS membranes function as mechanically encoded interfaces that direct macrophage morphology, motility, functional activation, and inflammatory polarization. More broadly, this study identifies substrate mechanical as a previously underappreciated regulator of macrophage mechanoimmunology and provides a useful platform for biomaterials research, disease modeling, and drug screening.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"4 2","pages":"Article 100194"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148184855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical forces of beating heart suppress cancer growth","authors":"Tingting Li ,&nbsp;Yiyao Liu","doi":"10.1016/j.mbm.2026.100197","DOIUrl":"10.1016/j.mbm.2026.100197","url":null,"abstract":"<div><div>The cardiac vasculature is characterized by high pressure, high blood flow, and dense vascular branching, which may increase its exposure to circulating tumor cells (CTCs). However, both primary cardiac tumors and metastases are remarkably rare. This mechanism has remained poorly understood. A recent report by Ciucci and co-workers show that mechanical load in the heart inhibits cancer cell proliferation. Their work proposes that physiological mechanical stimuli is not merely a regulator of cancer progression, but also an intrinsic anticancer mechanism.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"4 2","pages":"Article 100197"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148231471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanosensitive reactive oxygen Species:A precision medicine target for oxidative stress-related diseases","authors":"Kai Huang","doi":"10.1016/j.mbm.2026.100193","DOIUrl":"10.1016/j.mbm.2026.100193","url":null,"abstract":"<div><div>Oxidative stress induced by abnormal mechanical stress is a common pathological mechanism underlying the initiation and progression of various injury and diseases. Mechanosensitive reactive oxygen species (mechano-ROS), a subset of ROS specifically elicited by mechanical stress, are primarily generated from distinct sources including NADPH oxidases (NOXs), mitochondrial electron transport chain (ETC), uncoupled endothelial nitric oxide synthase (eNOS), and xanthine oxidase (XO/XOR) in a disease-specific manner. These mechano-ROS act as critical signaling mediators that link aberrant mechanical cues to cellular dysfunction, inflammation, barrier disruption, and disease progression. Scavenging excessive reactive oxygen species (ROS) has thus emerged as a key strategy for mitigating injury and disease progression. However, the primary enzymatic systems and cellular sources responsible for ROS generation differ across diseases, which may partly account for the limited clinical efficacy of broad-spectrum antioxidant therapies. Consequently, targeted interventions that identify and inhibit disease-specific major ROS sources, in combination with ROS-scavenging strategies, could synergistically reduce oxidative stress by both upstream source suppression and downstream ROS clearance. This approach offers promising avenues for the precision attenuation/treatment of different injury and diseases.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"4 2","pages":"Article 100193"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148184856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanobiology of hypertrophic chondrocyte mineralization: Biomechanical regulation and therapeutic implications in skeletal disorders","authors":"Yuhao Liu ,&nbsp;Guangyu Xu ,&nbsp;Yi Shen ,&nbsp;Shaotian Fu ,&nbsp;An Qin","doi":"10.1016/j.mbm.2026.100196","DOIUrl":"10.1016/j.mbm.2026.100196","url":null,"abstract":"<div><div>Chondrocyte proliferation, differentiation and hypertrophic mineralization are central events that guide subsequent vascular invasion and bone replacement processes. This process is controlled by a sophisticated molecular network including transcription factors such as SOX9 and Runx2, as well as key signaling pathways such as Bone Morphogenetic Protein (BMP), Indian Hedgehog (Ihh) and Fibroblast Growth Factor (FGF). Dysregulation of this network due to genetic mutations or metabolic deficiencies can disrupt mineralization, which underpins aberrant skeletal biomechanics properties. Therefore, understanding the physiological and pathological mechanisms governing chondrocyte proliferation, differentiation and mineralization holds significant potential for developing novel therapeutic strategies for disorders with compromised skeletal biomechanics.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"4 2","pages":"Article 100196"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148231487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanochemical bistability as a principle of robust morphogenesis","authors":"Shi-Lei Xue","doi":"10.1016/j.mbm.2026.100195","DOIUrl":"10.1016/j.mbm.2026.100195","url":null,"abstract":"<div><div>Embryogenesis is governed by diverse physical forces, yet how these forces coordinate with biochemical signals to ensure reproducible morphogenesis remains poorly understood. Using the developing vertebrate intestine as a model, recent studies integrating organoid systems, biophysical modeling, and pharmacological perturbations reveal that mechanochemical bistability, arising from feedback between actomyosin tension and luminal pressure, confers robust and irreversible crypt budding. This bistability ensures crypt morphology is tightly controlled during morphogenesis but becomes insensitive to fluctuations upon completion. In vivo, transient villus enterocyte swelling reduces epithelial tension and activates a cPLA₂-dependent mechanosensitive pathway in stem cells, synchronizing contractility across neighboring crypts and preventing competitive divergence. Together, these findings establish a multi-tiered coordination strategy in which global tissue mechanics couple with local mechanosensation to buffer variability and enforce convergent morphogenesis. Mechanochemical bistability, coupled with tissue-level mechanical coordination, may represent a general principle underlying robust and reproducible patterning across developmental and organoid systems.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"4 2","pages":"Article 100195"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148231376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A tailored fit: How intermediate filaments orchestrate glioblastoma invasion","authors":"Jessy V. van Asperen ,&nbsp;Elly M. Hol","doi":"10.1016/j.mbm.2026.100174","DOIUrl":"10.1016/j.mbm.2026.100174","url":null,"abstract":"<div><div>Glioblastoma (GBM) is a highly invasive tumour. Invasion of GBM cells into the densely packed brain parenchyma reflects a profound mechanobiological adaptation to the mechanical constraints of the brain. A recent study by van Bodegraven et al. (<span><span>https://doi.org/10.1016/j.celrep.2025.116553</span><svg><path></path></svg></span>) positions intermediate filaments as central regulators of this mechanoadaptive response. The intermediate filament perinuclear cage decreases the deformability of the cell and therewith the deformability of the nucleus. Despite of this, the presence of intermediate filaments leads to a greater invasive capacity due to mechanosensitive upregulation of metalloproteinase 14 and increased extracellular matrix degradation. The enrichment of intermediate filament transcripts in GBM patient cells with pro-invasive markers indicates that intermediate filaments contribute to the specialization of GBM cells towards invasive behavior. This work fits within an emerging paradigm in which intermediate filament expression is viewed as being tailored to the mechanical demands of the invading cell.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"4 1","pages":"Article 100174"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress fiber traction force reshapes chromatin accessibility and YAP binding to direct diverse transcriptional programs in mesenchymal stem cells","authors":"Jiacheng Lei ,&nbsp;Yicen Long ,&nbsp;Xiaojing Liu ,&nbsp;Zhiqin Chu ,&nbsp;Qiang Wei","doi":"10.1016/j.mbm.2026.100178","DOIUrl":"10.1016/j.mbm.2026.100178","url":null,"abstract":"<div><div>Stress fiber–generated traction forces critically regulate mesenchymal stem cell (MSC) behavior, yet how mechanical cues are integrated across transcriptional programs remains unclear. Here, we attenuated actomyosin contractility in human MSCs and performed parallel Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq), YAP-targeted Cleavage Under Targets and Tagmentation sequencing (CUT&amp;Tag) and RNA-seq profiling. We show that reduced stress fiber traction force selectively reorganizes chromatin accessibility into coherent functional modules, resulting in diverse transcriptional programs. The mechanosensitive co-activator YAP functions as a parallel force-responsive regulatory layer coordinating with chromatin accessibility changes. Integration of chromatin accessibility, YAP occupancy, and transcriptomic profiles reveals pathway-specific regulatory responses, identifying focal adhesion and PI3K-Akt signaling as central mechanosensitive pathways coordinated across layers. Together, these findings establish a modular framework for force-dependent gene regulation, demonstrating how mechanical signals are integrated across epigenomic and transcriptional networks to shape MSC transcriptional programs.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"4 1","pages":"Article 100178"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}