Bone Abstracts

Previous studies demonstrated a negative influence of the growth- and differentiation factor midkine (MDK) on bone formation during bone remodeling and fracture healing. Additionally, MDK-deficiency protected mice from a loss of trabecular bone mass after ovariectomy (OVX). Therefore, we hypothesized that MDK may also be involved in the pathogenesis of delayed, osteoporotic fracture healing after OVX in mice. Thus, we analyzed the expression of MDK during bone regeneration and...

Objectives: Maternal vitamin D status in pregnancy is associated with neonatal bone mass, and altered DNA methylation. Mice exposed to early life vitamin D deficiency have lower bone mass and reduced bone accrual in response to mechanical loading. Using tibias from these mice we assessed DNA methylation of promoters of genetic loci important for bone growth and development.Methods: C57/BL6 mice received a vitamin D replete or deplete diet for 6 weeks per...

Collagen XV is a secreted proteoglycan localized in the outermost layer of the basement membrane and in the fibrillar matrix. Previously, the collagen XV gene (COL15A1) has been linked to osteogenic differentiation, being identified mainly in mature osteoblasts forming new bone tissue or lining bone trabeculae. Our previous data on collagen XV knockout fetuses reports subtle skeletal changes. The aim of this study was to analyse skeletal changes in adult mice lacking collagen ...

In autosomal recessive osteopetrosis due to mutations of the TNFSF11 gene, deficiency of the pro-osteoclastogenic cytokine RANKL prevents osteoclast formation. RANKL is a membrane-bound protein cleaved into active soluble (s)RANKL by various enzymes, including metalloproteinase 14 (MMP14). We created a bio-device that released sRANKL and induced osteoclastogenesis in tnfsf11−/− mice. We tested various RANKL cell sources, and used mouse primary calvarial osteoblasts...

Ca2+ signaling and NFATc1 activation are essential for RANKL-induced osteoclast differentiation through the induction of Ca2+ oscillation, calcineurin activation, and translocation of NFATc1 into the nucleus. Homer proteins are scaffold proteins that have been proposed to modulate multiple Ca2+ signaling proteins, including inositol 1,4,5-triphosphate receptors, ryanodine receptors, transient receptor potential channels. In this study, we inves...

Angiogenesis and osteogenesis are tightly linked and dependent on each other. Lipocalin 2 (LCN2) is a mechanoresponding adipokine, strongly upregulated in osteogenic cells subjected to microgravity (0.08–0.008 g), in which it impairs osteogenesis and upregulates the osteoclastogenic cytokine, RANKL. We investigated the role of LCN2 in the crosstalk between angiogenesis and osteogenesis in simulated microgravity conditions as a model of mechanical unloading. Mouse and huma...

Background: Isotretinoin has demonstrated efficacy in a wide range of disorders. The beneficial effects of the drug, however, are limited by its adverse impact on the bone. Children exposed to high doses are at risk for premature epiphyseal closure, while adults on long-term therapy have an increased tendency to develop hyperostosis and other changes of the bone. Presenting feature and Clinical management A 9-month-old infant presented with vomiting and distended abdomen due t...

Fracture healing is a multistep process that involves many cell lineages and is still not fully understood. We aimed to identify and characterize population of mesenchymal progenitor cells during its commitment within a fracture callus. To identify and trace cells in periosteum and bone marrow we used αSMA promoter-driven inducible Cre expression (αSMA-CreERT2) combined with a Cre-activated tdTomato reporter (Ai9) to generate αSMACre/Ai9 mice. Tibias, fixed with...

Bone is the primary site of metastasis for breast cancer, which leads mainly to osteolytic lesions, Cancer cells can expand into the bone for their ability to ‘dialogue’ with resident cells, interfering with the physiological processes of bone turnover. In this study, a large-scale analysis comparing gene expression of biopsies of bone and visceral metastases from human breast cancer patients showed that the receptor (G protein-coupled) activity modifying protein-2 (...

Objectives: In the modern society, all individuals are exposed throughout life to a variety of chemicals, which may contribute significantly to the human disease burden. Most of these chemicals are transferred to the fetus in-utero and to the infant via mother’s milk. Until recently, few studies have addressed effects of chemicals on the development of mineralized tissues following exposure during these early stages of life. In this experimental study, we analyse...