Volume 6 · Number 2 · June 2014
- Analysis of epigenetic modifications in bone cells: osteoblasts are osteoblasts isolated from bone a good model to study changes in DNA methylation [33-34]
- Comparative epigenomic analysis of bone tissue and primary osteoblasts [35-39]
- Risk of major osteoporotic or hip fracture in patients with cerebrovascular accident in the acute phase. Multicentre prospective study [40-45]
- Comparison of the osteogenic actions of parathyroid hormone-related protein (PTHrP) in diabetic and insulin-like growth factor-I (IGF-I) deficient mouse models [46-56]
Analysis of epigenetic modifications in bone cells: osteoblasts are osteoblasts isolated from bone a good model to study changes in DNA methylation?
Epigenetics is the study of the mechanisms which regulate gene expression in a stable and hereditary way, but without altering the DNA sequence 1. This field of research has gained importance in recent years and it is postulated that it may explain the process of differentiation of bone cells, the appearance of bone metabolic diseases, as well the inheritability of certain pathologies (for recent reviews, see 1-3). Epigenetic mechanisms include post-translational modification in histones, regulation of protein synthesis by means of microRNA and DNA methylation.read more
Objectives: Epigenetic mechanisms, and in particular cytosine methylation in the promoter regions, modulate the expression of many genes. However, their role in skeletal homeostasis has scarcely been studied. In particular, it is not known if the patterns of methylation of bone cells in culture are a good reflection of that which occurrs in bone tissues. The aim of this work was to explore the possible differences in cytosine methylation in human bone and in osteoblasts.
Material and methods: To achieve this we carried out a genome-wide study, analysing the degree of methylation of 23,667 loci and comparing the results in samples of bone tissue and in cultures of primary osteoblasts.
Results: Overall, we observed a good correlation between the two sample types, both in the whole group of loci (r2=0,87; p<10-50), and in those located in genes involved in bone metabolism. However, some of the loci (7-8%) deviated from this general tendency and showed differences in methylation greater than 20%.
Conclusions: These results indicate that the methylation data obtained in cultures are not necessarily a true reflection of that which occurs in tissues, which means that care should be taken when extrapolating such results to an in vivo situation.
Risk of major osteoporotic or hip fracture in patients with cerebrovascular accident in the acute phase. Multicentre prospective study
Objetives: Hemiplegic patients are considered to be a population at risk of suffering osteoporotic fractures. The aim of this work is to understand the absolute risk of fragility fracture in patients with cerebrovascular accident (CVA) and the osteometabolic state of patients with ictus in the acute phase, as well as confirming if there are baseline differences compared to a control group without cerebrovascular pathology.
Patients and method: Multicentre prospective study carried out in five Spanish hospitals. Two groups were established: a) patients with ictus of less than three months development, and b) a control group from a population without cerebrovascular disease. History of fragility fractures, number of falls in the previous year, bone mineral density (BMD) in the hip, FRAX® index, determinations of biochemistry and bone markers – calcium, phosphorus, alkaline phosphatase, vitamin D, parathormone (PTH), and carboxy-terminal telopeptide of collagen type I (CTX) – were analysed.
Results: A total of 82 patients were studied: 50 patients with CVA and 32 controls. 12% of those patients with CVA had an increased risk of suffering a hip fracture, and 8% an increased risk of a major osteoporotic fracture. In the control group the risk was greater. The hemiplegic patients had BMD in the hip lower than those in the control group, although the differences in both variables were not statistically significant.
The levels of CTX were higher in patients with CVA, this being the sole determination which showed a statistical difference between the two groups studied.
Conclusions: The patients with CVA had values of markers for bone resorption (CTX) significantly higher and a BMD in the hip lower than those in the control group.
Comparison of the osteogenic actions of parathyroid hormone-related protein (PTHrP) in diabetic and insulin-like growth factor-I (IGF-I) deficient mouse models
Work scholarship with a Research Fellowship in Molecular Biology FEIOMM 2011.
Diabetes mellitus (DM) is a metabolic pathology characterised by chronic hyperglycemia due to a deficit in the production and/or action of insulin. DM, above all type I, is commonly associated with osteopenia/osteoporosis and with an increased risk of fractures. Insulin-like growth factor-I (IGF-I), a factor abundant in the bone matrix which plays a significant role in the development and maintenance of bone mass, diminishes with DM. Parathyroid hormone-related protein (PTHrP), a modulator of growth and osteoblast function, acts on osteoprogenitors, promoting osteoblast differentiation and bone regeneration. Its expression is reduced in the presence of DM. In this work we have evaluated and compared the osteogenic actions of PTHrP in mouse models with type 1 DM and IGF-I deficiency. Diabetic mice by injection of streptozotocin had a reduction in bone mass in the long bones associated with an increase in oxidised proteins and a reduction in the expression of genes related to the Wnt pathway and of β-catenin protein, as well as alterations in vertebral trabecular bone. In the mouse model with IGF-I deficit our results indicate the presence of osteopenia both in the femur (associated with an inhibition of the Wnt pathway) and the spine (L1-L5). Our findings demonstrate that the administration of PTHrP, predominantly through its N-terminal domain, modulates the canonical Wnt pathway in relation to its osteogenic actions in a diabetic situation and also, in part, in the absence of IGF-I.read more
The classical functions of bone are the maintenance of phosphorus-calcium homeostasis, damage repair, as well its structural function which allows locomotion and protects the vital organs. The recent discovery of new functions for bone in the regulation of energy metabolism suggest that bone may be an endocrine organ.
In the last decade, different genetic and molecular studies carried out in mice have determined that osteocalcin increases the secretion of insulin, and sensitivity to it, by increasing the secretion of adiponectin, stimulates the proliferation and the better functioning of the beta cells, promotes the reduction of fatty mass and an increase in the consumption of energy.
These findings demonstrate the existence of a reciprocal regulation between bone and energy metabolism, mediated by osteocalcin. The recognition of the metabolic role of osteocalcin is a significant discovery in the field of osteology and endocrinology, bringing the possibility of new therapies in the treatment and prevention of metabolic diseases such as diabetes mellitus, sarcopenia, obesity and osteoporosis.
We introduce a new, special type of document, in which, within the Journal itself, we will debate a currently controversial theme which will allow the reader to reflect and, above all, participate by contributing their opinions in the form of letters to the Editor.
On this occasion, we address the matter of treatment holidays, using a clinical case. Two reasoned opinions, in favour and against, are expounded below, with the sole aim of setting out the arguments and stimulating the contribution of readers to the debate.read more