Bone Abstracts

Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein that controls the engulfment of apoptotic cells and exerts anti-inflammatory effects. It has been implicated in the pathogenesis of several diseases, but its role in the bone microenvironment is still unknown. Here we tested the hypothesis that MFG-E8 also regulates bone metabolism and the development of arthritis.MFG-E8 expression was detected in mouse bones and primary murine osteobl...

Introduction: Bone metastases represent a frequent complication of breast cancer and are characterized by increased tumour-driven activation of osteoclasts and subsequent bone loss. Aminobisphosphonates inhibit osteoclast function and are established therapies of skeletal metastases. Similar to statins, they block the mevalonate pathway and are thought to have direct anti-tumour effects. Here, we report on the anti-tumour potential of a sequential inhibition of the mevalonate ...

Introduction: Collagen and glycosaminoglycans (GAGs) such as hyaluronan (HA) and chondroitin sulfate (CS) are basic elements of bone structure and collagen-GAG composites are currently developed for a wide range of applications. Here, we report on the molecular and cellular effects of GAGs and their sulfated derivatives on osteocytes, which are fundamental orchestrators of bone remodeling.Materials and methods: The effects of native and sulfate-modified ...

The osteoclast-associated receptor (OSCAR), primarily described as a co-stimulatory regulator of osteoclast differentiation, represents a novel link between bone metabolism and vascular biology. Previously, we identified OSCAR on endothelial cells responding to the proatherogenic factor oxidized low density lipoprotein (oxLDL). Additionally, OSCAR expression was increased in the aorta of atherogenic apoE-knock-out (apoE-KO) mice, where it was further induced by feeding a high-...

Postmenopausal women with early stage hormone-receptor-positive breast cancer (EBC) are standardly treated with aromatase inhibitors (AIs). However, one side-effect of AIs treatment is a decrease in bone mineral density (BMD) and an increased risk of fracture. The objectives of this study were to examine: i) changes in bone formation (N-terminal propeptide of type I procollagen; PINP) and bone resorption (cross-linked C-telopeptides of bone type I collagen; CTX) markers, as we...

Osteoporosis is a frequent disease leading to an increased risk of fractures caused by a systemic impairment of bone mass, strength, and microarchitecture. Given the emerging role of the Wnt signaling pathway in bone biology, we focused on the function of the important Wnt inhibitor dickkopf-1 (Dkk-1) and examined how the deletion of Dkk-1 solely in osteoblasts or osteocytes influences bone homeostasis. Therefore, we used the Cre-LoxP recombination system and crossed Dkk-1-flo...

Breast cancer is the most frequent malignancy in women and frequently results in osteolytic bone metastases. Amino-bisphosphonates are a standard bone protective therapy and, similarly to statins, inhibit the mevalonate pathway that is crucial for posttranslational protein modifications (farnesylation and geranylation). Direct anti-tumor effects of amino-bisphosphonates and statins have been suggested but high concentrations are necessary to achieve meaningful effects. Our stu...

Wnt proteins and their cognate receptors play a significant role in malignant diseases, in particular in prostate cancer (PCa). We previously showed that WNT5A inhibits PCa cell proliferation and induces apoptosis in vitro, leading to reduced PCa growth in vivo. However, the involved receptors remain unknown. Here, we determine the role of two Wnt receptors (FZD8, RYK) and their influence on the WNT5A-induced effects on PCa cells.The ex...

Aims: Using an extensive bioinformatic approach we identified integrin α5 subunit as a novel potential target to treat bone dissemination from breast cancer. Aim of this study is to confirm the value of this target.Methods: Integrin α5 mRNA expression levels were quantified by qRT-PCR, using radically resected primary tumors of 427 breast cancer patients. α5 expression at protein level by IHC on primary tumor was correlated, in an addition...

Destructive bone lesions due to osteolytic bone disease (OBD) are a major cause of morbidity and mortality in multiple myeloma (MM) patients and the development of new therapeutic strategies is of great interest. In this study, we assessed the effect of SRC inhibition with saracatinib (AZD0530, AstraZeneca) on the development of MM and its associated OBD. We first determined SRC family kinase expression in the MM microenvironment and found that myeloma cells express SRC at low...