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Abstract Skeletal development depends on coordinated angiogenesis and osteogenesis. Bone morphogenetic proteins direct bone formation in part by activating SMAD1/5 signaling in osteoblasts. However, the role of SMAD1/5 in skeletal endothelium is unknown. Here, we found that endothelial cell-conditional SMAD1/5 depletion in juvenile mice caused metaphyseal and diaphyseal hypervascularity, resulting in altered trabecular and cortical bone formation. SMAD1/5 depletion induced excessive sprouting and disrupting the morphology of the metaphyseal vessels, with impaired anastomotic loop formation at the chondro-osseous junction. Endothelial SMAD1/5 depletion impaired growth plate resorption and, upon long-term depletion, abrogated osteoprogenitor recruitment to the primary spongiosa. Finally, in the diaphysis, endothelial SMAD1/5 activity was necessary to maintain the sinusoidal phenotype, with SMAD1/5 depletion inducing formation of large vascular loops and elevated vascular permeability. Together, endothelial SMAD1/5 activity sustains skeletal vascular morphogenesis and function and coordinates growth plate remodeling and osteoprogenitor recruitment dynamics in juvenile mouse bone.

Abstract Obesity adversely affects bone and fat metabolism in mice and humans. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been shown to improve glucose metabolism and bone homeostasis in obesity. However, the impact of omega-3 PUFAs on bone marrow adipose tissue (BMAT) and bone marrow stromal cell (BMSC) metabolism has not been intensively studied yet. In the present study we demonstrated that omega-3 PUFA supplementation in high fat diet (HFD + F) improved bone parameters, mechanical properties along with decreased BMAT in obese mice when compared to the HFD group. Primary BMSCs isolated from HFD + F mice showed decreased adipocyte and higher osteoblast differentiation with lower senescent phenotype along with decreased osteoclast formation suggesting improved bone marrow microenvironment promoting bone formation in mice. Thus, our study highlights the beneficial effects of omega-3 PUFA-enriched diet on bone and cellular metabolism and its potential use in the treatment of metabolic bone diseases.

Abstract Cochlear implant restores hearing loss through electrical stimulation of the hearing nerve from within the cochlea. Unfortunately, surgical implantation of this neuroprosthesis often traumatizes delicate intracochlear structures, resulting in loss of residual hearing and compromising hearing in noisy environments and appreciation of music. To avoid cochlear trauma, insertion techniques and devices have to be adjusted to the cochlear microanatomy. However, existing techniques were unable to achieve a representative visualization of the human cochlea: classical histology damages the tissues and lacks 3D perspective; standard microCT fails to resolve the cochlear soft tissues; and previously used X-ray contrast-enhancing staining agents are destructive. In this study, we overcame these limitations by performing contrast-enhanced microCT imaging (CECT) with a novel polyoxometalate staining agent Hf-WD POM. With Hf-WD POM-based CECT, we achieved nondestructive, high-resolution, simultaneous, 3D visualization of the mineralized and soft microstructures in fresh-frozen human cochleae. This enabled quantitative analysis of the true intracochlear dimensions and led to anatomical discoveries, concerning surgically-relevant microstructures: the round window membrane, the Rosenthal’s canal and the secondary spiral lamina. Furthermore, we demonstrated that Hf-WD POM-based CECT enables quantitative assessment of these structures as well as their trauma.

The authors present cryogenic contrast-enhanced MicroCT (cryo-CECT), which by freezing stained samples at optimal freezing rates improves the visualization of the tissue microstructure. They demonstrate quantitative 3D analysis of individual tissue constituents, such as muscle and collagen fibers.