Analysis of RAMP3 gene polymorphism with body composition and bone density in young and elderly women.

Background And Aim: The Receptor Activity Modifying Proteins (RAMPs) are a group of accessory proteins, of which there are three in humans, that interact with a number of G-protein coupled receptors (GPCR) and play various roles in regulation of endocrine signaling. Studies in RAMP3 knockout (KO) mice reveal an age related phenotype with altered metabolic regulation and high bone mass. To translate these findings into a clinically relevant perspective, we investigated the association between gene variants, body composition and bone phenotypes in two population-based cohorts of Swedish women.

Analysis of RAMP3 gene polymorphism with body composition and bone density in young and elderly women.

Background And Aim: The Receptor Activity Modifying Proteins (RAMPs) are a group of accessory proteins, of which there are three in humans, that interact with a number of G-protein coupled receptors (GPCR) and play various roles in regulation of endocrine signaling. Studies in RAMP3 knockout (KO) mice reveal an age related phenotype with altered metabolic regulation and high bone mass. To translate these findings into a clinically relevant perspective, we investigated the association between RAMP3 gene variants, body composition and bone phenotypes in two population-based cohorts of Swedish women.

Alzheimer's disease pathogenesis: Is there a role for folate?

Epigenetic modifications, including changes in DNA methylation, have been implicated in a wide range of diseases including neurological diseases such as Alzheimer's. The role of dietary folate in providing methyl groups required for maintenance and modulation of DNA methylation makes it a nutrient of interest in Alzheimer's. Late onset Alzheimer's disease is the most common form of dementia and at present its aetiology is largely undetermined.

Methyl Donor Status Influences DNMT Expression and Global DNA Methylation in Cervical Cancer Cells.

Background: Methyl donor status influences DNA stability and DNA methylation although little is known about effects on DNA methyltransferases. The aim of this study was to determine whether methyldonor status influences DNA methyltransferase (Dnmt) gene expression in cervical cancer cells, and if so, whether there are associated effects on global DNA methylation.

Materials And Methods: The human cervical cancer cell line, C4 II, was grown in complete medium and medium depleted of folate (FM+) and folate and methionine (FM).

Physiology of Bone.

Bone serves three main physiological functions: its mechanical nature provides support for locomotion and offers protection to vulnerable internal organs, it forms a reservoir for the storage of calcium and phosphate in the body, and it provides an environment for bone marrow production and haematopoietic cell development. The traditional view of bone as a passive tissue that responds to hormonal and dietary influences has changed over the past half century to one of bone as a dynamic adaptive tissue that responds to mechanical demands. This chapter gathers together some recent advances in bone physiology and molecular cell biology and discusses the potential application of the functional adaptation of bone to loading to enhance bone strength during childhood and adolescence.

Lack of prolidase causes a bone phenotype both in human and in mouse.

The degradation of the main fibrillar collagens, collagens I and II, is a crucial process for skeletal development. The most abundant dipeptides generated from the catabolism of collagens contain proline and hydroxyproline. In humans, prolidase is the only enzyme able to hydrolyze dipeptides containing these amino acids at their C-terminal end, thus being a key player in collagen synthesis and turnover.

The transient receptor potential ion channel TRPV6 is expressed at low levels in osteoblasts and has little role in osteoblast calcium uptake.

Background: TRPV6 ion channels are key mediators of regulated transepithelial absorption of Ca2+ within the small intestine. Trpv6-/- mice were reported to have lower bone density than wild-type littermates and significant disturbances in calcium homeostasis that suggested a role for TRPV6 in osteoblasts during bone formation and mineralization. TRPV6 and molecules related to transepithelial Ca2+ transport have been reported to be expressed at high levels in human and mouse osteoblasts.

Physiology of bone.

Bone serves three main physiological functions. Its mechanical nature provides support for locomotion and offers protection to vulnerable internal organs, it forms a reservoir for storage of calcium and phosphate in the body, and it provides an environment for bone marrow and for the development of haematopoietic cells. The traditional view of a passive tissue responding to hormonal and dietary influences has changed over the past half century to one of a dynamic adaptive tissue responding to mechanical demands.

The peroxisome proliferator activator receptor alpha/delta agonists linoleic acid and bezafibrate upregulate osteoblast differentiation and induce periosteal bone formation in vivo.

We showed previously that some actions of prostaglandin E(2) (PGE(2)) on bone are caused by its degradation product, PGA(2), which mediates its effects via a class of nuclear receptors known as the peroxisome proliferator activator receptors (PPARs), suggesting that the PPARs may be involved in the regulation of bone formation. The aims of this study were to determine the effects of PPARalpha/delta agonists on bone in vitro and in vivo. PPAR agonists were examined in vitro using the fibroblastic colony-forming unit (CFU-f) assay.

CMT3 alters mitochondrial function in murine osteoclast lineage cells.

Chemically modified tetracyclines (CMTs 1-10) were developed as non-antibiotic inhibitors of matrix metalloproteinases (MMPs). We previously demonstrated that MMP inhibition alone is insufficient to explain the pro-apoptotic action of CMTs in osteoclast lineage cells and we have explored additional mechanisms of action. We compared the characteristics of apoptosis in RAW264.

Failure to repair the c.338C>T mutation in carnitine palmitoyl transferase 2 deficient skin fibroblasts using chimeraplasty.

Chimeraplasty, using oligonucleotides to target gene repair, was heralded as an efficient alternative approach to conventional gene therapy. We designed oligonucleotides to target a common mutation in the carnitine palmitoyl transferase 2 gene and developed a specific and sensitive assay to detect gene repair in human skin fibroblasts homozygous for the mutation. We failed to repair the gene under a variety of conditions and believe this approach is of little value until cellular DNA repair mechanisms are much better understood.