Bone Abstracts

Medial vascular calcification (MVC) is a pathological condition common to a variety of diseases, including chronic kidney disease, diabetes, obesity, generalized arterial calcification of infancy, arterial calcification due to deficiency of CD73, and Keutel syndrome. These diseases share the common feature of tissue-nonspecific alkaline phosphatase (TNAP) upregulation in the vasculature. We developed a mouse model that overexpresses human TNAP in vascular smooth muscle cells, ...

IκB Kinase β (IKKβ), a key component of NFκB signaling, plays an important role in bone disease and cancer. Genetic and pharmacological inhibition of IKKβ/NFκB signaling increase bone mass and protect against ovariectomy- and inflammation-induced bone loss. Here, we describe a previously unknown role of the IKKβ/FoxO3a axis in bone metastasis associated with breast cancer. We observed that IKKβ expression is prevalent in invasive breast ...

Breast cancer (BrCa) patients with metastases restricted to bone (BO) show a longer overall survival compared to BrCa patients developing bone and visceral metastases (BV). To unveil the molecular mechanisms that segregate these two BrCa patient groups, we performed microarray analyses on bone metastasis samples from BO and BV patients, finding in the latter a set of up-regulated genes involved in oxygen metabolism. We focused on Hemoglobin B (HBB) and evaluated its expression...

Prostate cancer (PCa) is the most common cancer type in older men and often metastasizes to bone in advanced stages. Wnt proteins are implicated in carcinogenesis and especially WNT5A has been discussed to influence the clinical outcome of various cancer types, including PCa. In addition, WNT5A stimulates osteogenic differentiation and may thus not only be involved in PCa development, but also in the formation of subsequent skeletal metastasis. Here, we determined the role of ...

Recent studies confirmed the role of WNT16 in bone mineral density (BMD), bone strength and fracture risk. These findings made WNT16 interesting for further genetic and functional studies to clarify its effect on osteoporosis related parameters.A WNT16 candidate gene association study was performed in men from the Odense Androgen Study (OAS). Five tagSNPs and one multimarker test were selected for genotyping to cover most of th...

Gene deletion or treatments with a cathepsin K (CatK) inhibitor in mature preclinical models result not only result in lower bone resorption but also in higher bone formation (BF) on both remodeling and modeling surfaces. Although increased production of clastokines and matrix-derived growth factors may explain the increased BF at remodeling surfaces, the mechanisms for greater BF at modeling surfaces, including the periosteum, remain unexplained. We hypothesized that the abse...