Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2021.09.21.461298

Perilacunar bone tissue exhibits sub-micrometer modulus gradation which depends on the recency of osteocyte bone formation

Rux, C. J.·Vahidi, G.·Darabi, A.·Cox, L. M.·Heveran, C. M.
View original source ↗Export metadata ↓

Abstract

Osteocytes are capable of resorbing and replacing bone local to the lacunar-canalicular system (LCS remodeling). However, the impacts of these processes on perilacunar bone quality are not understood. It is well established that aging is associated with reduced whole-bone fracture resistance, reduced osteocyte viability, and truncated LCS geometries, but it remains unclear if aging changes perilacunar bone quality. In this study, we employed atomic force microscopy (AFM) to quantify sub-micrometer gradations from 2D maps surrounding osteocyte lacunae in young (5 mo) and aged (22 mo) female mice. AFM-mapped lacunae were also imaged with confocal laser scanning microscopy to determine which osteocytes had recently deposited bone as determined by the presence of fluorochrome labels. These assays allowed us to quantify gradations in nanoscale mechanical properties of bone-forming/non-bone-forming osteocytes in young and aged mice. This study reports for the first time that there are sub-micrometer gradations in modulus surrounding lacunae and that these gradations are dependent upon recent osteocyte bone formation. Perilacunar bone adjacent to bone-forming osteocytes demonstrated lower peak and bulk modulus values when compared to bone near non-bone-forming osteocytes from the same mouse. Bone-forming osteocytes also showed increased perilacunar modulus variability. Age reduced lacunar size but did not significant effect modulus gradation or variability. In general, lacunar morphology was not a strong predictor of modulus gradation patterns. These findings support the idea that lacunar-canalicular remodeling activity changes the material properties of surrounding bone tissue on a sub-micrometer scale. Therefore, conditions that affect osteocyte health have the potential to impact bone quality. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=62 SRC="FIGDIR/small/461298v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1fe5a68org.highwire.dtl.DTLVardef@1e17e90org.highwire.dtl.DTLVardef@13c2e3corg.highwire.dtl.DTLVardef@1ff9f38_HPS_FORMAT_FIGEXP M_FIG C_FIG

Explore related subjects

physiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Rux, C. J., Vahidi, G., Darabi, A., Cox, L. M., Heveran, C. M.. 2021-09-24. Perilacunar bone tissue exhibits sub-micrometer modulus gradation which depends on the recency of osteocyte bone formation. https://doi.org/10.1101/2021.09.21.461298

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

KEEP EXPLORING

Related preprints

bioRxiv2026

Trunk muscle activity across various trunk-limb coordination patterns in centipede locomotion

Animals coordinate movements of their limbs and flexible bodies, yet how trunk muscle activity changes across locomotor patterns remains unclear. We simultaneously recorded electromyograms from trunk muscles (deep dorsal oblique muscles) and trunk-limb kinematics in two centipede species exhibiting retrograde and direct locomotor waves during swimming and walking. During swimming, trunk muscle activity followed a similar phase relationship with trunk bending in both species despite opposite wave directions and different involvement of limbs, suggesting common active generation of undulation. During fast walking, trunk muscle activity was strongest around the ipsilateral swing phase in the undulatory retrograde-wave gait of Scolopendra mutilans, but weaker and associated with the ipsilateral stance phase despite the nearly straight trunk in the direct-wave gait of Scolopocryptops rubiginosus. Together, our findings suggest that the same trunk muscles serve two contrasting mechanical roles depending on locomotor mode: either generating trunk undulation or actively straightening the trunk against limb-induced deformation.

physiology↗
bioRxiv2026

Quantifying and Visualizing the Invisible Hazard of Infant Rebreathing

BACKGROUND: Rebreathing of expired gases during prone infant sleeping contributes to hypoxic and hypercapnic exposure, even without airway obstruction. We investigated how anatomical, physiological, and environmental factors influence aerodynamic rebreathing. METHODS: A dynamically scaled in vitro model simulated prone nasal breathing corresponding to infants weighing 2 to 5 kg, with nostril diameters of 3.2 to 6.0 mm and breathing frequencies of 25 to 40 breaths/min. Ambient temperature and sleep-surface characteristics were varied. Rebreathing was quantified using tracer measurements, while flow visualization revealed the underlying aerodynamic mechanisms. RESULTS: Rebreathing exceeded 60% despite unobstructed nasal openings. Increasing ambient temperature from 23 to 30 degrees C increased rebreathing by 68 to 77%, while reducing simulated infant mass from 5 to 2 kg increased rebreathing by 39 to 46%. Fibrous surfaces increased rebreathing, particularly near inclined nasal openings. A novel finding was that increasing nostril diameter from 3.2 to 6.0 mm increased rebreathing by up to 50%. Flow visualization revealed vortical structures that retained expired fluid near the nasal openings, facilitating re-inspiration. CONCLUSIONS: Aerodynamic rebreathing depends strongly on simulated infant characteristics and sleeping environments. These findings are consistent with established safe-sleep recommendations and identify nostril diameter, for the first time, as a potentially important anatomical factor warranting clinical investigation.

physiology↗
bioRxiv2026

Epigenetic Rescue of Disuse Muscle Atrophy by Histone Deacetylase Inhibitor Trichostatin A

Mechanical unloading rapidly induces skeletal muscle atrophy and functional deterioration, yet how the loss of mechanical input influences nuclear architecture, chromatin organization, and associated transcriptional programs remains poorly understood. Here, we investigated whether pharmacological inhibition of histone deacetylases (HDACs) using Trichostatin A (TSA) could attenuate the consequences of continued mechanical unloading in a murine hindlimb suspension model. Following 14 days of unloading, mice exhibited impaired locomotor activity, altered muscle architecture, and widespread transcriptional reprogramming characterized by increased expression of atrophy associated genes, inflammatory mediators, and extracellular matrix remodeling pathways, alongside suppression of mitochondrial metabolic programs. Super resolution imaging further revealed irregular Lamin A/C organization and disruption of discrete H3K9me3 associated heterochromatin foci. Systemic TSA treatment significantly attenuated the decline in locomotor activity, accompanied by trends toward reduced body weight loss, and preservation of muscle morphology. Transcriptomic analysis demonstrated a substantial shift toward the baseline expression profile, with high-dose TSA attenuating FOXO associated catabolic programs, inflammatory, and extracellular matrix-related signatures, while enhancing mitochondrial oxidative phosphorylation pathways. Quantitative gene level and pathway analyses further revealed dose dependent and selective reversal of unloading associated transcriptional changes. Notably, TSA treatment also partially preserved nuclear lamina organization and the focal distribution of H3K9me3 associated heterochromatin. Despite these muscle specific benefits, TSA did not prevent trabecular bone loss over the 14-day unloading period, although several muscle-expressed genes potentially involved in muscle to bone communication were altered by treatment. Together, these findings demonstrate that HDAC inhibition counteracts multiple functional and molecular consequences of skeletal muscle unloading and is associated with partial preservation of nuclear and heterochromatin organization. This study supports a link between mechanical unloading, nuclear architectural remodeling, and HDAC sensitive transcriptional regulation, providing a foundation for epigenetic strategies to counter disuse induced muscle deterioration.

physiology↗