Inhibition of FGF23 is a therapeutic strategy to target hematopoietic stem cell niche defects in β-thalassemia.

Clinical evidence highlights a relationship between the blood and the bone, but the underlying mechanism linking these two tissues is not fully elucidated. Here, we used β-thalassemia as a model of congenital anemia with bone and bone marrow (BM) niche defects. We demonstrate that fibroblast growth factor 23 (FGF23) is increased in patients and mice with β-thalassemia because erythropoietin induces FGF23 overproduction in bone and BM erythroid cells via ERK1/2 and STAT5 pathways.

Angiotensin II Modulates Calcium/Phosphate Excretion in Experimental Model of Hypertension: Focus on Bone.

A link between hypertension and long-term bone health has been suggested. The aim of this study was to investigate the effects of chronic angiotensin II administration on urinary calcium/phosphate excretion, bone mineral density, bone remodeling and osteoblast population in a well-established experimental model of hypertension, in the absence of possible confounding factors that could affect bone metabolism. Male Sprague-Dawley rats, divided in the following groups: (a) Angiotensin II (Ang II, 200 ng/kg/min, osmotic minipumps, sub cutis, = 8); (b) Ang II+losartan (Los, 50 mg/kg/day, , = 6); (c) control group (physiological saline, sub cutis, = 9); and (d) control+losartan ( = 6) were treated for four weeks.

Enhanced p53 Levels Are Involved in the Reduced Mineralization Capacity of Osteoblasts Derived from Shwachman-Diamond Syndrome Subjects.

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities, caused by loss-of-function mutations in the gene, a factor involved in ribosome biogenesis. By analyzing osteoblasts from SDS patients (SDS-OBs), we show that SDS-OBs displayed reduced gene expression and reduced/undetectable SBDS protein compared to osteoblasts from healthy subjects (H-OBs). SDS-OBs cultured in an osteogenic medium displayed a lower mineralization capacity compared to H-OBs.

Bone and body composition analyses by DXA in adults with GH deficiency: effects of long-term replacement therapy.

Purpose: The effects of growth hormone (GH) replacement on bone mass and body composition in adult with GH deficiency (AGHD) are still debated with regard to their persistence in the long term. Moreover, the impact of the gender on the response to GH is controversial. Aim of this study was to evaluate the long-term effects of rhGH replacement on bone mass and body composition in a monocentric cohort of patients with AGHD.

Serum Irisin May Predict Cardiovascular Events in Elderly Patients With Chronic Kidney Disease Stage 3-5.

Objective: Irisin is a circulating myokine released from skeletal muscles after physical exercise. Irisin production decreases during the course of chronic kidney disease (CKD) as a potential consequence of sarcopenia and physical inactivity.

Methods: This observational study explored the relationship of serum irisin with cardiovascular outcome in 79 patients with stage 3-5 CKD.

Glucagon-like peptide-1 receptor and sarcoglycan delta genetic variants can affect cardiovascular risk in chronic kidney disease patients under hemodialysis.

Background: Chronic kidney disease (CKD) patients under hemodialysis show a higher risk of cardiovascular (CV) mortality and morbidity than the general population. This study aims to identify genetic markers that could explain the increased CV risk in hemodialysis.

Methods: A total of 245 CKD patients under hemodialysis were recruited and followed up for 5 years to record CV events.

Hematopoietic stem cell function in β-thalassemia is impaired and is rescued by targeting the bone marrow niche.

Hematopoietic stem cells (HSCs) are regulated by signals from the bone marrow (BM) niche that tune hematopoiesis at steady state and in hematologic disorders. To understand HSC-niche interactions in altered nonmalignant homeostasis, we selected β-thalassemia, a hemoglobin disorder, as a paradigm. In this severe congenital anemia, alterations secondary to the primary hemoglobin defect have a potential impact on HSC-niche cross talk.

The Role of Growth Hormone in Mesenchymal Stem Cell Commitment.

Growth hormone (GH) is best known for its prominent role in promoting prepubertal growth and in regulating body composition and metabolism during adulthood. In recent years, the possible role of GH in the modulation of mesenchymal stem cell (MSC) commitment has gained interest. MSCs, characterized by active self-renewal and differentiation potential, express GH receptors.

Short-term evaluation of cardiac morphology, function, metabolism and structure following diagnosis of adult-onset growth hormone deficiency.

Objective: The impact of growth hormone (GH) deficiency of the adult on cardiovascular function remains only partially elucidated. Purpose of this study was to test cardiac function in adult GH deficient patients using cardiac magnetic resonance (CMR).

Design: Cardiac magnetic resonance (CMR) techniques, including cardiac P MR spectroscopy and evaluation of gadolinium late-enhancement, were applied to assess simultaneously, in a cross-sectional fashion, morphological, functional, metabolic, and structural parameters of the left (LV) and right ventricle (RV) in 15 patients with adult onset GH deficiency.

L-Carnitine Reduces Oxidative Stress and Promotes Cells Differentiation and Bone Matrix Proteins Expression in Human Osteoblast-Like Cells.

Bone fragility and associated fracture risk are major problems in aging. Oxidative stress and mitochondrial dysfunction play a key role in the development of bone fragility. Mitochondrial dysfunction is closely associated with excessive production of reactive oxygen species (ROS).

Calcium fluxes at the bone/plasma interface: Acute effects of parathyroid hormone (PTH) and targeted deletion of PTH/PTH-related peptide (PTHrP) receptor in the osteocytes.

Calcium ion concentration ([Ca]) in the systemic extracellular fluid, ECF-[Ca], is maintained around a genetically predetermined set-point, which combines the operational level of the kidney and bone/ECF interfaces. The ECF-[Ca] is maintained within a narrow oscillation range by the regulatory action of Parathyroid Hormone (PTH), Calcitonin, FGF-23, and 1,25(OH)D. This model implies two correction mechanisms, i.

GH prevents adipogenic differentiation of mesenchymal stromal stem cells derived from human trabecular bone via canonical Wnt signaling.

The imbalance between osteogenesis and adipogenesis, which naturally accompanies bone marrow senescence, may contribute to the development of bone-associated diseases, like osteoporosis. In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium.

Betaine promotes cell differentiation of human osteoblasts in primary culture.

Background: Betaine (BET), a component of many foods, is an essential osmolyte and a source of methyl groups; it also shows an antioxidant activity. Moreover, BET stimulates muscle differentiation via insulin like growth factor I (IGF-I). The processes of myogenesis and osteogenesis involve common mechanisms with skeletal muscle cells and osteoblasts sharing the same precursor.

Evidence for Altered Canonical Wnt Signaling in the Trabecular Bone of Elderly Postmenopausal Women with Fragility Femoral Fracture.

Wnt signaling, a major regulator of bone formation and homeostasis, might be involved in the bone loss of osteoporotic patients and the consequent impaired response to fracture. Therefore we analyzed Wnt-related, osteogenic, and adipogenic genes in bone tissue of elderly postmenopausal women undergoing hip replacement for either femoral fracture or osteoarthritis. Bone specimens derived from the intertrochanteric region of the femurs of 25 women with fracture (F) and 29 with osteoarthritis without fracture (OA) were analyzed.

Intestinal Calcium Absorption among Hypercalciuric Patients with or without Calcium Kidney Stones.

Background And Objectives: Idiopathic hypercalciuria is a frequent defect in calcium kidney stone formers that is associated with high intestinal calcium absorption and osteopenia. Characteristics distinguishing hypercalciuric stone formers from hypercalciuric patients without kidney stone history (HNSFs) are unknown and were explored in our study.

Design, Setting, Participants, & Measurements: We compared 172 hypercalciuric stone formers with 36 HNSFs retrospectively selected from patients referred to outpatient clinics of the San Raffaele Hospital in Milan from 1998 to 2003.

Modifications of the mouse bone marrow microenvironment favor angiogenesis and correlate with disease progression from asymptomatic to symptomatic multiple myeloma.

While multiple myeloma (MM) is almost invariably preceded by asymptomatic monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering MM (SMM), the alterations of the bone marrow (BM) microenvironment that establish progression to symptomatic disease are circumstantial. Here we show that in Vk*MYC mice harboring oncogene-driven plasma cell proliferative disorder, disease appearance associated with substantial modifications of the BM microenvironment, including a progressive accumulation of both CD8 and CD4 T cells with a dominant T helper type 1 (Th1) response. Progression from asymptomatic to symptomatic MM was characterized by further BM accrual of T cells with reduced Th1 and persistently increased Th2 cytokine production, which associated with accumulation of CD206Tie2 macrophages, and increased pro-angiogenic cytokines and microvessel density (MVD).

Ghrelin Increases Beta-Catenin Level through Protein Kinase A Activation and Regulates OPG Expression in Rat Primary Osteoblasts.

Ghrelin, by binding growth hormone secretagogue receptor (GHS-R), promotes osteoblast proliferation but the signaling mechanism of GHS-R on these cells remains unclear. Since canonical Wnt/β-catenin pathway is critically associated with bone homeostasis, we investigated its involvement in mediating ghrelin effects in osteoblasts and in osteoblast-osteoclast cross talk. Ghrelin (10(-10)M) significantly increased β-catenin levels in rat osteoblasts (rOB).

Role of plaque calcification regulators osteoprotegerin and matrix Gla-proteins in stable angina and acute myocardial infarction.

Aim: To assess serum levels of the plaque calcification regulators osteoprotegerin (OPG) and Matrix Gla-proteins (MGP) in individuals with stable angina and acute myocardial infarction submitted to coronary angiography and their relation to coronary artery disease burden.

Methods: The study included 40 individuals affected by ST-elevation myocardial infarction (STEMI) and 40 individuals with stable angina who all underwent coronary angiography, with evaluation of the extent of coronary artery disease by Syntax Score calculation and measurement of serum OPG and MGP levels. Osteoporosis was excluded by femoral and vertebral computerized bone mineralometry.

Serum dioxin concentrations and bone density and structure in the Seveso Women's Health Study.

Background: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is a known endocrine disruptor. In animal studies, TCDD exposure impairs bone metabolism and increases fragility. To our knowledge, no epidemiologic studies have examined this association.

Painful prosthesis: approaching the patient with persistent pain following total hip and knee arthroplasty.

Background: Symptomatic severe osteoarthritis and hip osteoporotic fractures are the main conditions requiring total hip arthroplasty (THA), whereas total knee arthroplasty (TKA) is mainly performed for pain, disability or deformity due to osteoarthritis. After surgery, some patients suffer from "painful prosthesis", which currently represents a clinical problem.

Methods: A systematic review of scientific literature has been performed.

Optimal dietary calcium intake in HIV treated patients: no femoral osteoporosis but higher cardiovascular risk.

Background & Aims: We performed a cross-sectional study on adult HIV-infected patients, on HAART, without calcium or vitamin D supplementation to evaluate if the cardiovascular risk or the presence of osteoporosis may be predictive factors of an optimal daily calcium intake (DCI>1000 mg/day).

Methods: Patients underwent a dual-energy X-ray absorptiometry, measured biochemical parameters and compiled a validated questionnaire for the assessment of DCI. Osteoporosis (OP) was defined according to the WHO classification at either the vertebral spine or femoral neck.

Vitamin D levels and risk of multiple sclerosis in patients with clinically isolated syndromes.

Background: Growing evidence suggests that vitamin D deficiency may be one of the most important environmental factors for the development of multiple sclerosis (MS).

Objectives: The objectives of this paper are to evaluate serum 25-hydroxyvitamin D (25(OH)D) levels in patients with clinically isolated syndromes (CIS) and to examine whether they are related to MS risk.

Methods: This is a retrospective study of 100 CIS patients hospitalized from 2000 to 2009 at San Raffaele Hospital, Milan, Italy.