YAP regulates periosteal expansion in fracture repair DOI Creative Commons
Madhura P. Nijsure, Brendan Tobin, Dakota L. Jones

и другие.

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

Опубликована: Дек. 23, 2024

Bone fracture repair initiates by periosteal expansion. The periosteum is typically quiescent, but upon fracture, cells proliferate and contribute to bone repair. expansion of the regulated gene transcription; however, molecular mechanisms behind are unclear. Here, we show that Yes-Associated Protein (YAP) transcriptional coactivator with PDZ-binding motif (TAZ) mediate cell proliferation. increases number YAP-expressing cells, deletion YAP TAZ from Osterix (Osx) expressing impairs early Mechanistically, regulates both 'cell-intrinsic' 'cell-extrinsic' factors allow for Specifically, identified Morphogenetic 4 (BMP4) as a extrinsic factor YAP, rescues impairment YAP/TAZ deletion. Together, these data establish mediated induce in stages provide new putative targets therapeutic interventions.

Язык: Английский

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
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.

Developmental Dynamics, Год журнала: 2025, Номер unknown

Опубликована: Май 13, 2025

Abstract Background Bones develop to structurally balance strength and mobility. Bone developmental dynamics are influenced by whether an animal is ambulatory at birth. Precocial species, which birth, advanced skeletal maturity in utero experience postnatal development under mechanical loading. Here, we characterized bone the lower forelimbs of precocial goats using microcomputed tomography histology. Our analysis focused on two phalanges 1 (P1) bones partially fused metacarpal goat autopod from birth through adulthood. Results P1 cortical densified rapidly after but thickness increased continually Upon normalization body mass, normalized polar moment inertia was constant over time, suggestive changes correlating with trabecular number until sexual (12 months), while trabeculae grew primarily thickening. Unlike prenatal synostosis (i.e., fusion) diaphysis, epiphyses occurred postnatally, prior growth plate closure, a unique fibrocartilaginous endochondral ossification. Conclusions These findings implicate loading identify novel event caprine epiphysis.

Язык: Английский

Процитировано

0
Insights into the bone morphogenetic protein signaling in musculoskeletal disorders: Mechanisms and crosstalk DOI Creative Commons
Bo Chen, Xu Liu, Min Hu

и другие.

Journal of Orthopaedic Translation, Год журнала: 2025, Номер 52, С. 419 - 440

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
Mechanical effects in aging of the musculoskeletal system: Molecular signaling and spatial scale alterations DOI Creative Commons

Zeyuan Zhang,

F. Cao, Dingfa Liang

и другие.

Journal of Orthopaedic Translation, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
The yes-associated protein-1 (YAP1) inhibitor celastrol suppresses the ability of transforming growth factor β to activate human gingival fibroblasts DOI Creative Commons

Angha Naik,

Pratyusha Chitturi,

John Nguyen

и другие.

Archives of Oral Biology, Год журнала: 2024, Номер 160, С. 105910 - 105910

Опубликована: Фев. 5, 2024

To determine whether celastrol, an inhibitor of the mechanosensitive transcriptional cofactor yes-associated protein-1 (YAP1), impairs ability TGFβ1 to stimulate fibrogenic activity in human gingival fibroblast cell line. Human fibroblasts were pre-treated with celastrol or DMSO followed by stimulation without (4 ng/ml). We then utilized bulk RNA sequencing (RNAseq), real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, proliferation assays if impaired TGFβ1-induced responses a Celastrol induce expression profibrotic marker and mediator CCN2. Bulk RNAseq analysis treated TGFβ1, presence absence revealed that mRNA genes within extracellular matrix, wound healing, focal adhesion cytokine/Wnt signaling clusters. RT-PCR extracted RNAs confirmed antagonized anticipated contribute fibrotic responses. also reduced proliferation, YAP1 nuclear localization response TGFβ1. inhibitors such as could be used impair pro-fibrotic fibroblasts.

Язык: Английский

Процитировано

2
Effect of low‐intensity pulsed ultrasound on the mineralization of force‐treated cementoblasts and orthodontically induced inflammatory root resorption via the Lamin A/C‐Yes associated protein axis DOI
Fu Zheng, Tong Wu,

Feifei Wang

и другие.

Journal of Periodontal Research, Год журнала: 2024, Номер unknown

Опубликована: Авг. 2, 2024

Abstract Aims Orthodontic treatment commonly results in orthodontically induced inflammatory root resorption (OIIRR). This condition arises from excessive orthodontic force, which triggerslocal responses and impedes cementoblasts' mineralization capacity. Low‐intensity pulsed ultrasound (LIPUS) shows potential reducing OIIRR. However, the precise mechanisms through LIPUS reduces OIIRR remain unclear. study aimed to explore effects of on force‐treated cementoblasts its impact Methods We established a rat model locally administered stimulation for 7 14 days. analyzed volume, osteoclast differentiation, expression osteocalcin yes‐associated protein 1 (YAP1) using micro‐computed tomography (micro‐CT), hematoxylin eosin, tartrate‐resistant acid phosphatase, immunofluorescence immunohistochemistry staining. In vitro, we applied compressive force immortalized mouse (OCCM30). assessed alkaline phosphatase (ALP) staining, alizarin red real‐time quantitative polymerase chain reaction, Western blotting Results rats, reduced OIIRR, as evidenced by micro‐CT analysis histological enhanced OCCM30 cells, indicated ALP upregulated mRNA mineralization‐related genes, increased markers. Mechanistically, activated YAP1 signaling via cytoskeleton‐Lamin A/C pathway, supported blot analysis. Conclusion demonstrates that promotes activating cytoskeletal‐Lamin pathway. These findings provide fresh insights into how benefits suggest strategies preventing treating

Язык: Английский

Процитировано

2
Blood and bones: Mechanical cues and Hippo signaling drive vascular invasion during limb formation DOI Creative Commons
Marc N. Wein

Developmental Cell, Год журнала: 2024, Номер 59(2), С. 173 - 174

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

1
Cyr61 delivery promotes angiogenesis during bone fracture repair DOI Creative Commons
Annemarie Lang,

Emily A. Eastburn,

Mousa Younesi

и другие.

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

Опубликована: Апрель 6, 2024

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 regulated by mechanical cues during fracture repair. Here, we map the distribution endogenous Cyr61 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 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

1
Advances in skeletal genomics research across tissues and cells DOI Creative Commons
Genevieve Housman

Current Opinion in Genetics & Development, Год журнала: 2024, Номер 88, С. 102245 - 102245

Опубликована: Авг. 24, 2024

Phenotypic variation within the skeleton has biological, behavioral, and biomedical functional implications for individuals species. Thus, it is critical to understand how genomic, environmental, mediating regulatory factors combine interact drive skeletal trait development evolution. Recent research efforts clarify these mechanisms have been made possible by expanded collections of genomic phenotypic data from in vivo tissues, as well relevant vitro cell culture systems. This review outlines this current work recommends that continued exploration complexity should include an increased focus on interactions between physiologically contexts contribute at population evolutionary scales.

Язык: Английский

Процитировано

1