Unraveling the Mechano-Molecular Mechanisms of TRAP Activity Using CRISPR/Cas9 Mediated Fluorescent Reporter Mice

Yιlmaz, Dilara; Marques, Francisco Correia; Fischer, Yannick; Zimmermann, Sandra; Hwang, Gaonhae; Atkins, Penny R.; Mathavan, Neashan; Singh, Amit; Souza, Pedro Herculano Guimarães Ferreira de; Kuhn, Gisela; Wehrle, Esther; Müller, Ralph

doi:10.2139/ssrn.4476675

Cited by 1 publication

(1 citation statement)

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“…Our lab has previously established a bone cell reporter (BCR) mouse model using CRISPR/Cas9 technology to label osteoblast (Integrin binding sialoprotein - Ibsp) and osteoclast-specific targets (tartrate-resistant acid phosphatase (TRAP) type 5 - Acp-5) with fluorescent proteins (eGFP, mCherry) ( 75 ). All mice were bred, monitored and maintained under specific pathogen free (SPF) conditions at the ETH Phenomics Centre, ETH Zürich (12 h:12 h light-dark cycle, ad libitum access to maintenance feed and water).…”

Section: Methodsmentioning

confidence: 99%

Spatial Transcriptomics in Bone Mechanomics: Exploring the Mechanoregulation of Fracture Healing in the Era of Spatial Omics

Mathavan,

Singh,

Correia Marques

et al. 2024

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In over 100 years, the field of bone mechanobiology has sought experimental techniques to unravel the molecular mechanisms governing the phenomenon of mechanically-regulated bone (re)modelling. Each cell within a fracture site resides within different local micro-environments characterized by different levels of mechanical strain - thus, preserving the spatial location of each cell is critical in relating cellular responses to mechanical stimuli. Our spatial transcriptomics based "mechanomics" platform facilitates spatially-resolved analysis of the molecular profiles of cells with respect to their local in vivo mechanical environment by integrating time-lapsed in vivo micro-computed tomography, spatial transcriptomics, and micro-finite element analysis. We investigate the transcriptomic responses of cells as a function of the local strain magnitude by identifying the differential expression of genes in regions of high and low strain within a fracture site. Our platform thus has the potential to address fundamental open questions within the field and identify novel mechano-responsive targets to enhance bone regeneration.

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Section: Methodsmentioning

confidence: 99%