Bone Abstracts

The P2Y2 receptor is a G-protein-coupled receptor and the natural ligands (ATP/UTP) strongly inhibit mineralized bone nodule formation by osteoblasts in vitro. We have earlier shown that overexpression of the P2Y2 receptor in vivo resulted in decreased bone mineral density (BMD), partially due to increased bone resorption, but also decreased formation (detected by serum bone markers and bone histomorphometry).This ...

Low protein or low calcium intake are known to impair bone growth, but their combined effects on determinants of bone strength are not well understood. We investigated the influence of various protein and calcium containing diets on determinants of bone strength in growing rats.One-month-old female rats were fed isocaloric diets containing 10, 7.5 or 5% casein, with 1.1% (normal; NCa) or 0.2% calcium (low; LCa) during 8 weeks. Tibia midshaft geometry (ou...

There is a growing body of evidence indicating the important role of the neonatal steroid milieu in programming sexually dimorphic pattern in various physiological systems. We tested the hypothesis that abnormal exposure to steroid hormones within a critical developmental period elicits permanent changes on tooth eruption, enamel mineralization, and leptin and corticosterone concentrations in adulthood. Newborn Wistar rats were divided into four groups, two male groups and two...

An IgM monoclonal gammopathy (MGUS) is often the first sign of a lymphomonocytic B-lymphoma (Waldenström macroglobulinemia-WD). Osteolytic lesions can occur in B cell malignancies (WD, hairy cell leukemia, LLC\..) but are less frequent than in myeloma. In addition, bone remodeling in WD is poorly understood. However, an osteoporosis is often observed in MGUS patients. We studied a series of bone biopsies performed in patients with an IgM gammopathy by histomorphometry, mi...

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 (...

Receptor activity modifying proteins (RAMPs 1, 2 and 3) are a class of important accessory proteins that interact and regulate several G-protein coupled receptor (GPCR) activity by finely modulating ligand interaction and in some cases trafficking receptors to cell surface.Predominant roles of RAMPs include ligand selectivity in receptors for Calcitonin (CT) family of peptides that comprise calcitonin, calcitonin gene related peptide, amylin and Adrenome...

The G protein-coupled receptor, protease-activated receptor 2 (PAR2), is expressed by osteoblasts and required for normal skeletal growth and repair. Prostate cancer (PCa) cells commonly secrete proteolytic activators of PAR2 (including matriptase and kallikrein-related peptidase 4) and frequently form osteogenic metastases in bone. This study was undertaken to investigate the hypothesis that PAR2 activators released by PCa cells modulate osteo...

The biomineralization process is initiated inside matrix vesicles (MVs), with phosphate and calcium ions crystallizing as hydroxyapatite. This process is accomplished by the activities of several proteins, such as annexins (e.g. AnxV) that mediates Ca2+ influx into MVs and tissue-nonspecific alkaline phosphatase (TNAP), a phosphomonohydrolase that uses ATP and PPi as substrates. Dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS...

Constant remodeling of extracellular matrix (ECM) is a hallmark during physiological conditions, such as stem cell differentiation, embryogenesis and tissue repair. Matrix metalloproteinases (MMP) play a key role in these processes. MMPs, MMP-activator (EMMPRIN/CD147) and MMP-inhibitors (TIMPs and RECK) are responsible for bone matrix remodeling and, probably, determinate the level of its turnover. Mesenchymal stem cells derived from dental pulp are multipotent and have the ca...

Identifying novel molecules that enhance human skeletal (mesenchymal) stem cells (hMSC) differentiation into osteoblastic bone forming cells (OB), may lead to development of new bone anabolic drugs. We have identified Kix, a small molecule kinase inhibitor that enhanced ex vivo OB differentiation and reduced apoptosis of hMSC. We found that Kix targeted undifferentiated hMSC populations and not their differentiated progeny. In addition, Kix increased in vivo ...