Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.10.30.763214

Bone Response to Mechanical Loading is Highly Heritable and Correlates with Osteocyte Lacunar Morphology in Genetically Diverse Mouse Strains

Migotsky, N.·Lamia, S.·Shuster, J. T.·Kumar, S.·Farber, C. R.·Silva, M. J.
View original source ↗Export metadata ↓

Abstract

Skeletal loading is a key regulator of bone formation. Studies using in vivo loading of rodent bones have established many mechanical and biological factors that regulate bone response to loading. However, most studies have been performed in a small number of inbred rodent strains, and there are few data on effects of genetic background on the loading response. In the current study we employed two murine models of genetic diversity, the Diversity Outbred (DO) and their eight founder inbred strains, to assess the influence of genetic background on skeletal response to tibial loading. Loading-induced periosteal bone formation rates and formed bone volumes varied significantly among inbred mouse strains. DO mice, which each carry a unique mixture of alleles of the inbred founder strains, were more responsive to loading, on average, than the the inbred founder strains. Additionally, bone response to mechanical loading was highly heritable; broad-sense heritability for measures of periosteal formation were near or above 80%. Furthermore, osteocyte lacunar morphology correlated with loading response across inbred strains. Inbred 129S1 mice had the most elongated lacunae and exhibited the highest magnitude of response on both periosteal and endocortical surfaces. 129S1 also demonstrated a robust transcriptional response to loading, although the pathways induced by loading were largely conserved with lab-standard C57Bl/6. Together, these findings demonstrate that genetic background significantly contributes to bone response to loading and establish DO mice as a platform for discovery of genes that regulate skeletal mechanoresponsiveness.

Explore related subjects

bioengineeringPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Migotsky, N., Lamia, S., Shuster, J. T., Kumar, S., Farber, C. R., Silva, M. J.. 2026-11-02. Bone Response to Mechanical Loading is Highly Heritable and Correlates with Osteocyte Lacunar Morphology in Genetically Diverse Mouse Strains. https://doi.org/10.64898/2026.10.30.763214

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

1D model simulations suggest biofilms can suppress cathodic H2 bubble formation

Microbial electrosynthesis (MES) electrochemically generates H2 for the reduction of CO2 into acetate by acetogens. So far, the importance of a biofilm on the cathode of such systems remains under debate. Here, we investigated the role of cathodic biofilms through computational modelling. We developed MES-BIOFILM, a comprehensive one-dimensional model to simulate steady-state H2 and CO2 concentration gradients within cathodic biofilms, while accounting for the limited solubility of H2. The effects of key biofilm properties, including thickness, cell density and H2 consumption rate were analysed. Overall, our simulations indicate that cathodic biofilms play an important role in (1) minimizing H2 loss from the system through H2 consumption within the biofilm; and (2) suppressing H2 bubble formation by maintaining the H2 concentrations at the cathode surface below saturation. Our model predicts that the current density at which H2 bubbles begin to form can be increased by 5.5-fold relative to a bare electrode when biofilms exhibit a high cell density and high H2 consumption rate. This effect requires biofilms of at least 50 m thickness, whereas CO2 diffusion limitations arise above 200 m. These findings highlight the critical role of biofilms to increase MES performance, while requiring further experimental validation.

bioengineering↗
bioRxiv2026

RNA-triggered Cas12a2 antibacterial activity and resistance plasmid degradation

Antimicrobial resistance (AMR) necessitates programmable antibacterial strategies with novel mechanisms. Here, we evaluated an inducible intracellular CRISPR/Cas12a2 system in engineered Escherichia coli targeting a chloramphenicol-resistance (Chl) transcript. Cas12a2 activation significantly delayed bacterial growth and reduced recoverable colony-forming units (CFU) by 3-log10 in vitro, and reduced bacterial burdens in a mouse skin wound model. Transcriptomic profiling revealed upregulation of recA, a key mediator of the SOS response. We therefore designed a Chl-recA dual-targeting construct, which produced a greater growth delay than either single-targeting counterpart. The optimized dual-targeting system led to an approximately 4-log10 reduction in bacterial burden in vivo. Furthermore, exploratory qPCR of culture supernatants suggested a treatment-associated decrease in amplifiable plasmid DNA. Overall, this study provides proof-of-concept for resistance-transcript-guided Cas12a2 antibacterial activity and highlights the potential of co-targeting stress-associated transcripts to enhance programmable antimicrobials.

bioengineering↗
bioRxiv2026

Unlocking Targeted Underwater Delivery of Coral Probiotics

The rapid global decline of coral reefs has intensified the need for innovative conservation strategies, including microbial therapies to enhance coral health and resilience. A major limitation, however, is the lack of effective delivery systems for administering Beneficial Microorganisms for Corals (BMCs). In this study, we present natural, biodegradable systems for the underwater delivery of probiotic bacteria to corals. Three customized alginate-based delivery formats (beads, hydrogels, and filaments) were developed and loaded with the probiotic Pseudoalteromonas peptidolytica. The materials were loaded with the bacterium at an average concentration of 10^(4) CFU/g of dry polymer and engineered to sink underwater while keeping their structural integrity over time. In vitro assays showed controlled release kinetics, with encapsulated probiotics remaining viable and capable of replication. In vivo experiments compared syringe-based inoculation with the application of alginate beads, hydrogels, and filaments to corals. Microbiome analyses performed before and after inoculation confirmed successful probiotic colonization following deployment of the alginate-based delivery systems. Relative abundance of the probiotic genus Pseudoalteromonas increased markedly in treated corals, reaching 11.5 % after 48 h with alginate beads, 12.7 % after 48 h with hydrogels, and 12.6 % after 24 h with filaments. Furthermore, the degradation mechanisms of the three delivery systems were investigated. As the first biomaterial-based underwater delivery systems specifically engineered for coral probiotics, these alginate-based materials provide a promising foundation for advancing microbial therapies in both controlled aquaria and natural reef environments.

bioengineering↗