P2Y Receptors in Bone - Anabolic, Catabolic, or Both?

P2Y receptors, including eight subtypes, are G protein-coupled receptors that can be activated by extracellular nucleotides. Nearly all P2Y receptors are expressed in bone cells, suggesting their involvements in bone physiology and pathology. However, their exact roles in bone homeostasis are not entirely clear. Therefore, this mini review summarizes new research developments regarding individual P2Y receptors and their roles in bone biology, particularly detailing those which execute both anabolic and catabolic functions. This dual function has highlighted the conundrum of pharmacologically targeting these P2Y receptors in bone-wasting diseases. Further research in finding more precise targeting strategy, such as promoting anabolic effects via combining with physical exercise, should be prioritized.

[18F] Sodium Fluoride PET Kinetic Parameters in Bone Imaging

This report describes the significance of the kinetic parameters (k-values) obtained from the analysis of dynamic positron emission tomography (PET) scans using the Hawkins model describing the pharmacokinetics of sodium fluoride ([18F]NaF) to understand bone physiology. Dynamic [18F]NaF PET scans may be useful as an imaging biomarker in early phase clinical trials of novel drugs in development by permitting early detection of treatment-response signals that may help avoid late-stage attrition.

About biological hip joint prostheses and the biomechanical behavior of implanted femur

Biofidel femur Models with finite elements were developed using a specific segmentation combination with computed tomography and solid modeling tools capable of representing bone physiology and structural behavior. These biofidel Finite Element Models (FEM) are used to evaluate the change in the physiological distribution of stress in the prosthesis femur and to evaluate the new design criteria for biopsy biopsy biopsy biopsy. The proposed belief patterns allowed us to adequately take into account the non-isotropic features of the proximal femoral epiphysis and isotropic behavior in diaphysis to explain the critical changes in stress distribution in a femur resected after the implantation of a traditional articular prosthesis. It has been shown that a wide range of femoral diaphyses is completely protected by rigid prostheses that significantly alter the physiological distribution of stress, which should guarantee healthy growth and bone regeneration.

CLEAR ALIGNERS- A REVIEW ARTICLE

clear aligners are rapidly growing sector of orthodontic treatment. Increased esthetic perception and increased demand for orthodontic care from adults have contributed to demand for a more esthetic technique for orthodontic treatment. For diagnosis, therapeutic preparation, and designing the nal occlusal result, clear aligners use digital technology. Clear aligners allow the biomechanics to be optimized by staging tooth movements in a particular sequence in the software program. The rate of tooth movement can also be modied according to the bone physiology of the individual by adjusting the scheduled number of days for aligner adjustments, depending on the individual's bone physiology

Bone fragility in patients affected by congenital diseases non skeletal in origin

Background Bone tissue represents a large systemic compartment of the human body, with an active metabolism, that controls mineral deposition and removal, and where several factors may play a role. For these reasons, several non-skeletal diseases may influence bone metabolism. It is of a crucial importance to classify these disorders in order to facilitate diagnosis and clinical management. This article reports a taxonomic classification of non-skeletal rare congenital disorders, which have an impact on bone metabolism Methods The International Osteoporosis Foundation (IOF) Skeletal Rare Diseases Working Group (SRD-WG), comprised of basic and clinical scientists, has decided to review the taxonomy of non-skeletal rare disorders that may alter bone physiology. Results The taxonomy of non-skeletal rare congenital disorders which impact bone comprises a total of 6 groups of disorders that may influence the activity of bone cells or the characteristics of bone matrix. Conclusions This paper provides the first comprehensive taxonomy of non-skeletal rare congenital disorders with impact on bone physiology.

Genetic and atherosclerotic plaque immunohistochemical analyses do not associate reduced sclerostin expression with cardiovascular events

The sclerostin antibody romosozumab increases bone formation and decreases bone resorption, leading to increased bone mass, bone mineral density and bone strength, and reduced fracture risk. In a clinical study versus alendronate in postmenopausal women (ARCH), an imbalance in adjudicated serious cardiovascular (CV) events driven by an increase in myocardial infarction (MI) and stroke was observed.To investigate whether inhibition of sclerostin in atherosclerotic plaques may have contributed to this imbalance, sclerostin was immunostained in human plaques to determine whether it was detected in regions relevant to plaque stability. Additionally, genetic variants associated with lifelong reduced sclerostin expression were explored for associations with phenotypes including those related to bone physiology and CV risk factors/events in a population-based phenome-wide association study (PheWAS).Sclerostin expression was absent (67%) or reduced in atherosclerotic plaques and when present was in deeper regions of the plaque/wall and not in areas considered relevant to plaque stability (fibrous cap and endothelium). Natural genetic modulation of sclerostin by variants with a significant positive effect on bone physiology showed no association with lifetime risk of MI or stroke. These data do not support a causal association between sclerostin inhibition and increased risk of serious cardiovascular events.

Bone biomarkers in koalas: validation of assays and preliminary analyses

Traumatic injury, including bone fracture, is, to date, one of the leading causes of koala mortality in the South East Queensland region of Australia. Further, the specialist diet of koalas, which is restricted to certain Eucalyptus spp., may impact their normal bone physiology. Considering the dramatic koala population decline and high incidence of trauma, a greater understanding of koala bone physiology may support conservation. We retrieved from GenBank the protein sequences of parathyroid hormone (PTH), osteocalcin (OCN), and tissue-nonspecific alkaline phosphatase (TNALP) in human, dog, cattle, horse, koala, and gray short-tailed opossum. After homology was determined, plasma samples from 13 koalas were analyzed with human PTH, OCN, and bone-specific ALP (BALP) assay kits. Although koala PTH exhibited relatively low sequence homology with placental mammals, high sequence homology between humans and koalas was observed for both OCN and TNALP, and successful cross-reactivity was achieved using human enzyme immunoassay kits for detection of OCN and BALP biomarkers in koala plasma. However, we identified no correlation between OCN and BALP concentrations of healthy and trauma-affected koalas ( p = 0.66 and p = 0.79, respectively). Further analysis of OCN and BALP in healthy and diseased koalas will allow a better understanding of bone physiology in this unique marsupial.

Involvement of Noncoding RNAs in the Differentiation of Osteoclasts

As the most important bone-resorbing cells, osteoclasts play fundamental roles in bone remodeling and skeletal health. Much effort has been focused on identifying the regulators of osteoclast metabolism. Noncoding RNAs (ncRNAs) reportedly regulate osteoclast formation, differentiation, survival, and bone-resorbing activity to participate in bone physiology and pathology. The present review intends to provide a general framework for how ncRNAs and their targets regulate osteoclast differentiation and the important events of osteoclastogenesis they are involved in, including osteoclast precursor generation, early differentiation, mononuclear osteoclast fusion, and multinucleated osteoclast function and survival. This framework is beneficial for understanding bone biology and for identifying the potential biomarkers or therapeutic targets of bone diseases. The review also summarizes the results of in vivo experiments and classic experiment methods for osteoclast-related researches.