Evaluation of a CRISPR/Cas9-based dual-fluorescent reporter mouse model of premature aging to investigate the mechanobiology of bone regeneration

Mathavan, Neashan; Gregorio, Lorena; Yιlmaz, Dilara; Marques, Francisco Correia; Kuhn, Gisela; Müller, Ralph; Wehrle, Esther

doi:10.1016/j.bonr.2022.101349

Cited by 1 publication

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“…Micro-CT-based bone morphometric analysis confirmed the effect of cyclic mechanical loading with a significantly enhanced osteogenic response producing much larger callus / bone volumes. Although limited to n = 2 mice per group, this is corroborated by our previous studies in female 20-week-old C57BL/6 mice (11), female 12-week-old and 35-week-old PolgA D257A/D257A mice (65, 66) and female 12-week-old BCR:PolgA D257A/D257A mice (67). Moreover, as illustrated in Figure 2, sites of bone formation (identified in orange) unequivocally predominate between weeks 3 -5 in the mechanically loaded fracture sites.…”

Section: Discussionsupporting

confidence: 85%

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

Mathavan,

Singh,

Correia Marques

et al. 2024

Preprint

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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: Discussionsupporting

confidence: 85%