Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

In Vivo Evaluation of the Presence of Bone Marrow in Cortical Porosity in Postmenopausal Osteopenic Women

This is the first observational study examining cortical porosity in vivo in postmenopausal osteopenic women and to incorporate data from two different imaging modalities to further examine the nature of cortical porosity. The goal of this study was to combine high-resolution peripheral computed tomography (HR-pQCT) images, which contain high spatial resolution information of the cortical structure, and magnetic resonance (MR) images, which allow the visualization of soft tissues such as bone marrow, to observe the amount of cortical porosity that contains bone marrow in postmenopausal osteopenic women. The radius of 49 and the tibia of 51 postmenopausal osteopenic women (age 56 ± 3.7) were scanned using both HR-pQCT and MR imaging. A normalized mutual information registration algorithm was used to obtain a three-dimensional rigid transform which aligned the MR image to the HR-pQCT image. The aligned images allowed for the visualization of bone marrow in cortical pores. From the HR-pQCT image, the percent cortical porosity, the number of cortical pores, and the size of each cortical pore was determined. By overlaying the aligned MR and HR-pQCT images, the percent of cortical pores containing marrow, the number of cortical pores containing marrow, and the size of each cortical pore containing marrow were measured. While the amount of cortical porosity did not vary greatly between subjects, the type of cortical pore, containing marrow vs. not containing marrow, varied highly between subjects. The results suggest that cortical pore spaces contain components of varying composition, and that there may be more than one mechanism for the development of cortical porosity

Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation

Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to “Cafeteria diets" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity leading to Metabolic Syndrome

Adiposity and cancer risk: new mechanistic insights from epidemiology

Excess body adiposity, commonly expressed as body mass index (BMI), is a risk factor for many common adult cancers. Over the past decade, epidemiological data have shown that adiposity-cancer risk associations are specific for gender, site, geographical population, histological subtype and molecular phenotype. The biological mechanisms underpinning these associations are incompletely understood but need to take account of the specificities observed in epidemiology to better inform future prevention strategies

Adipose-derived stromal vascular fraction cells and platelet-rich plasma: Basic and clinical implications for tissue engineering therapies in regenerative surgery

Cell-based therapy and regenerative medicine offer a paradigm shift in regard to various diseases causing loss of substance or volume and tissue or organ damage. Recently, many authors have focused their attention on mesenchymal stem cells for their capacity to differentiate into many cell lineages. The most widely studied types are bone marrow mesenchymal stem cells and adipose derived stem cells (ADSCs), which display similar results. Based on the literature, we believe that the ADSCs offer advantages because of lower morbidity during the harvesting procedure. Additionally, platelet-rich plasma can be used in this field for its ability to stimulate tissue regeneration. The aim of this chapter is to describe ADSC preparation and isolation procedures, preparation of platelet-rich plasma, and the application of ADSCs in regenerative plastic surgery. We also discuss the mechanisms and future role of ADSCs in cell-based therapy and tissue engineering