Bone Abstracts

The development of optimally performing biomaterials mimicking the natural physiological processes underlying bone repair is essential for non-healing large bone lesions. We sought to develop scaffolds that fill the lesions and improve bone healing. We tested three scaffolds comprised of varying percentages of lactide (LA), caprolactone (CL), and methacrylate produced by two-photon photopolymerization; LCM 3 (8:2; 85%), 4 (9:1; 90%), and 6 (9:1; 40%). We hypothesized that the ...

The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined. Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis, and angiogenesis. In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ~8 days (d8) and is blunted in BSP...

In bone marrow, bone marrow stromal cells (BMSCs) have the capacity to differentiate into osteoblasts and adipocytes. Onset of osteoporosis with age stems in part from the enhanced bone marrow adipogenesis that represses osteogenesis. In this study, we demonstrate that disruption of nuclear factor I-C (NFI-C) impairs osteoblast differentiation and bone formation, and increases bone marrow adipocytes. Interestingly, NFI-C controls postnatal bone formation but does not influence...

Introduction: Despite the popularity of platet lysate (PL) treatments in orthopaedics, the mechanism of action and the effectiveness of this therapeutic tool is still controversial. So far, the activity of PL has been associated with different growth factors (GFs) released upon platelet degranulation. However, PL activity might also be due to the efficient cell to cell transport system of GF and other bioactive molecules by their encapsulation into exosomes. In this study, we ...

Limb length discrepancy has been observed in children with hemiplegic cerebral palsy (HCP). However, the difference of bone age and limb lengths have been a controversial issue. The purpose of this study was to analyze the bone age and the upper extremity segmental lengths between affected and naffected in HCP patients.Seventy-eight patients (39 boys and 39 girls; mean age 71.3±28.1 months). Fourty-five children were right and 33 were left hemiplegi...

Osteoporosis, as a global public health concern, may be induced by various hazardous substances such as cadmium (Cd) and pesticide diazinon (DZN). Selenium (Se), an essential trace element, can adversely modify bone structure in higher concentrations. The current study was designed to investigate structural changes in femoral bone of adult male rats after simultaneous co-administration to Cd, DZN, and Se. A total of 20 male Wistar rats were randomly divided into two experiment...

The aim of this study was to determine morphological and densitometric properties of lumbar vertebrae obtained from male and female silver foxes. Five lumbar vertebrae (L2–L6) were isolated from 1-year-old males (n=5) and females (n=6) and cleaned from remaining soft tissues to determine bone weight and vertebral body length. Quantitative computed tomography (QCT) and SOMATOM EMOTION SIEMENS apparatus (Siemens, Erlangen, Germany) were used to determine t...

The regeneration of traumatized, damaged or lost bone is still a major clinical and socio-economical problem. Bone-tissue engineering approaches involve culturing mesenchymal stem cells (MSCs) on scaffolds, in order to create a 3D microenvironment in which MSCs are able to generate functional tissues and regulate foreign body reaction to implanted construct. Excessive or non-resolving inflammation, characterized by the presence of monocytes, macrophages and giant cells, makes ...

One growth factor that potentially plays a role in fracture healing is midkine (Mdk). Mdk is expressed in chondrocytes during bone repair (Ohta et al. 1999) and has been shown to influence bone mass and mechanotransduction (Neunaber et al. 2010, Liedert et al. 2011). The aim of the present study was to evaluate the effects of Mdk-deficiency on bone repair in a standardized mouse femur osteotomy model.Mdk-deficient and wildtype ...

Human mesenchymal stromal cells (hMSC) have been investigated as a clinical therapy to promote tissue repair. However, the disappearance of grafted cells soon after engraftment suggests that hMSC could principally act as initiators of repair through paracrine mechanisms.The aim of this study was to evaluate the relative contribution of grafted hMSC and host cells in promoting bone tissue repair. We isolated hMSC from three bone marrow (BM) donors, then d...

Bone-tissue engineering approaches involve culturing mesenchymal stem cells (MSCs) on 3D scaffolds designed to mimic the composition, structure, and biomechanics of the native bone matrix. One of the key challenges in bone–tissue engineering is to understand the host response to implantable engineered constructs. Macrophages play an important role in fracture healing and tissue repair and are mainly involved in the inflammatory response at the early stage upon scaffold im...

This study was undertaken to evaluate the effect of whole-body vibration (WBV) with extremely low-amplitude on early-stage bone healing. Experiments were conducted with an approval of the Animal Research Committee of Osaka University Graduate School of Engineering Science. Male BALB/cByJJcl mice were subjected to a 0.5 mm drill-hole surgery on a tibial diaphysis at 14 weeks of age and divided into three groups (n=8 each) from the day after the surgery, which received ...

Postmenopausal women with forearm fracture have higher cortical porosity and lower trabecular density perhaps due to excessive age-related bone loss1. Remodelling becomes unbalanced and rapid only after ~45 years of age. We therefore proposed that bone fragility in premenopausal women with a forearm fracture originates during growth. At metaphyses, trabeculae emerging from the periphery of the growth plate form cortex by ‘corticalization’)2. We ...

Background: Alkaline phosphatase (ALP) has an essential role in bone mineralization. ALP is attached to the surface of matrix vesicles (MVs) in which hydroxyapatite crystals are initially formed. Formation of a tentative collagen–ALP complex may be an early step in the calcification process. The present study was designed to investigate the binding properties of different ALPs to collagen present in bone and cartilage, i.e. types 1 and 2 collagen.Me...

Although the heavy metal pollutant cadmium (Cd) is a well known teratogen, the mechanism behind Cd mediated teratogenicity is still unclear and it mainly targets the bone development. Previously we and other groups reported on the protective role of nitric oxide (NO), a key signaling molecule in the embryonic developmental process, against thalidomide and other teratogenic assaults also NO is considered to be a vital signaling molecule in the regulation of bone formation. The ...

Caspases are the basic enzymatic components in the apoptotic process. Recently, these molecules seem to participate not only in apoptotic but also in other cellular events, particularly in differentiation. This work aimed to further investigate novel roles of executive caspases such as caspase-7. The investigation is based on our previously published findings showing non-apoptotic roles of caspase-7 in odontogenesis.In this study, we followed the localiz...

Caspase-7 belongs to executive apoptotic and pro-inflammatory caspases. Recent reports point to novel roles of these caspases, particularly in cell differentiation. As we revealed such function of caspase-7 in odontogenesis, we turned our attention to participation of this molecule in formation of hard tissue in general.In this work, both type of bones, intramembranous (mandibular/alveolar bone), and endochondral (long bones) were investigated. Mouse hea...

Growth plate cartilage is solely responsible for bone lengthening in children. Injury upon growth plate is often repaired by bony tissue which leads to bone growth defects such as limb length discrepancies or bone angulation deformity at later life. Earlier studies using an established rat growth plate injury model have identified a series of repair phases; inflammatory, fibrogenic, osteogenesis and remodelling repair phases. Currently, the cellular and molecular mechanisms in...

Glucocorticoids are the most commonly used drugs in medical therapy, released in stress and necessary for normal development in both humans and animals.The aim of this study was to investigate the effect of prenatally administered dexamethasone (Dex), a synthetic glucocorticoid, on the histomorphometry of the femur in the offsprings of spiny mice, as a precocial species, characterized by high fertility, and the rapid development of the fetal, allowing th...

We assessed whether systemic Strontium ranelate (SrRan) administration accelerates the healing of a bone defect and could modulate local bone cellular activities. Proximal tibia bone defects were created in 6-month-old female rats, which received then orally SrRan (625 mg/kg per day, 5/7 days) or vehicle (controls) for 4, 8, or 12 weeks. Bone samples were analysed by micro-computed tomography and histomorphometry in various compartments, ie metaphyseal second spongiosa (MC), a...

Caspases belong to cysteine proteases participating in apoptosis and inflammation. However, there is recent evidence about their functions also in other events such as cell differentiation. This is supported also by our latest research of odontogenesis and osteogenesis. With the increasing interest in caspases due to their apoptosis-related therapies but also emerging non-apoptotic roles, exact evaluation of their impact at single cell level becomes challenging.<p class="a...

BMP6 is a member of the TGFβ superfamily with a high potential to induce new bone formation. Recently, we discovered that blood coagulum from the patient’s own blood (WBCD) modified with calcium salts serves as an appropriate autologous carrier for BMPs (OSTEOGROW device). Preclinical experiments indicate that BMP6 is efficacious when used in a significantly lower amounts than BMP2 and BMP7. Besides testing its osteogenic activity, we also tested the influence of the...

To evaluate the regeneration of alveolar bone after treatment with bone-resorption inhibitors in old acyclic rats that had been through a long period of low estrogen. Thirty-two female Wistar rats with 20 months old intact and ovariectomized (OVX at 4 months of age), were randomized into four groups (n=8/group): i) intact; ii) OVX/O (corn oil); iii) OVX/E2 (17β-estradiol, 400 μg) and iv) OVX/RLX (Raloxifene, 1 mg/kg per day). All treatments began ...

Among activation of apoptotic machinery, Fas (CD95)/FasL (CD178) were suggested to act in cell proliferation and differentiation. Expression of Fas and FasL was reported during tooth and bone formation. The examination of gld mice showed increased total body bone mass and number of osteoblasts in long bones. However, Fas and FasL functions in osteogenesis remain controversial. As most of studies dealing with Fas/FasL system in bone formation were performed in endochondral mode...

Alterations in fetal nutrition result in developmental adaptations that permanently alter the structure, physiology and metabolism of the offspring. β-hydroxy-β-methylbutyrate (HMB) is the bioactive metabolite of leucine responsible for inhibiting proteolysis and for modulating protein turnover in vitro and in vivo.The aim of the study was to determine the effect of maternal administration with HMB on mineralization, geometry ...

It is known that body weight is positively correlated with increased bone mineral density and decreased fracture risk. Adiponectin is expressed in bone forming cells, and administration of adiponectin has been demonstrated to stimulated osteoblast proliferation. The overall role of adiponectin in bone metabolism remains unrevealed as both stimulated and inhibiting effects on osteoclastogenesis have been reported. We aimed at describing the relationship between adiponectin and ...

The proper healing of bone defects requires a bone graft or bone substitute and synthetic materials have been developed as alternatives to autografts and allografts. Poly(DL-lactic-co-glycolic acid) (PLGA) is a synthetic polymer widely used for bone healing because of its biocompatibility and biodegradability. PLGA scaffolds have also been used in drug delivery devices, such as in combination with simvastatin, to stimulate bone growth. In this work, we examined ...

Aim: To evaluate progression of bone mineral density (BMD) and bone mineral content (BMC) during pubertal development and influence of body composition and vitamin D on BMD and BMC in children and adolescents.Materials and methods: This cross-sectional study was part of an ongoing health survey of Delhi school children. Total 1905 apparently healthy school children (835 boys; and 1070 girls) in the age group of 6–17 years were studied. After brief h...

The aim of this study was to determine interrelationships between final body weight, bone-specific alkaline phosphatase (BAP), IGF1 and morphological, densitometric and mechanical properties of deciduous mandibular teeth isolated from seven healthy Polish Merino rams. Four incisors (I1–I4) and second premolar (P2) were obtained from 5-month-old sheep. Teeth were cleaned, weighed, and their length was measured. Mean volumetric tooth mineral...

Introduction: Fragility fractures are number growing. They reduced quality life and increased mortality. After 50 years, one woman and two men will have an osteoporotic fracture in their lifetime. The presence of a vertebral fracture (VF) multiplied the risk of new vertebral fracture and the risk of hip fracture. They are pauci or asymptomatic.Study purpose: Evaluate the prevalence of fragility vertebral fractures after 50 years, the number of asymptomat...

Pentraxin 3 (PTX3) is a highly conserved member of the long pentraxins subfamily produced in response to proinflammatory stimuli. Its biological roles have been associated to infection, female fertility and angiogenesis. We aimed to elucidate the role of PTX3 in the process of fracture healing.WT mice and mice deficient for the PTX3 gene (PTX3-KO) were used, after obtaining the approval from the Ethical committee. Cells from bone marrow and endosteal/per...

Osteoporotic fractures are very common and represent an enormous unmet medical need. Our group has previously reported that addition of rTNF to the fracture site promotes fracture healing in C57/BL6 mice (Glass et al. PNAS 2011). Using a murine fracture model of endochondral healing, we observed that local addition of rTNF only accelerates fracture repair if administered within the first 24 h following injury. The optimal therapeutic dose is 1 ng. TNF is firs...

Members of the Rho family including small GTPase Cdc42 have been shown to play multiple roles in cell regulation, including regulation of cytoskeletal organization, cell migration, proliferation, and apoptosis. However, their tissue-specific roles in vivo, especially in limb bud mesenchyme, remain largely unknown. Herein, we report that conditional deletion of Cdc42 in AER dose not change the limb development, however, knockout of Cdc42 in mesenchymal stem cells of li...

Patients with hypoparathyroidism lack sufficient parathyroid hormone (PTH) and exhibit reduced bone turnover, abnormally increased bone mineral density (BMD), and abnormal bone microarchitecture. Current treatment regimens fail to address underlying PTH deficiency. In the REPLACE phase III trial, treatment with rhPTH(1–84) restored mineral homeostasis, increased bone turnover markers (BTMs), and decreased BMD in patients with hypoparathyroidism.REPE...

The analysis of intact parathyroid hormone (PTH) (PTH1–84) is useful in the diagnosis of hyper- and hypocalcaemia, hyperparathyroidism, and in the prevention of bone mineral disorders in renal patients. However, the analysis is complicated by the presence of PTH fragments. These are especially prone to accumulation in renal failure, and cross-react differently with different immunoassays, including the most recent, third-generation immunoassays. As such, large variability...

Recombinant human parathyroid hormone (rhPTH) (1–84) is currently being developed as PTH replacement therapy for patients with hypoparathyroidism. Because rhPTH(1–84) is administered subcutaneously, we compared the pharmacokinetic profile of PTH(1–84) and the calcemic response following S.C. rhPTH(1–84) injection in thigh and abdomen.In this phase 1, open-label, three-way crossover study, healthy postmenopausal women received three ra...

Introduction: Elevated FGF-23 serum levels are induced by hyperphosphatemia and are linked to poor skeletal mineralization and adverse outcomes including vascular calcification and mortality. Recently, it was shown that FGF-23 levels are substantially elevated in acute kidney injury (AKI), and that higher levels in AKI are associated with a greater risk of adverse outcomes.Methods: In 25 vitamin D deficient (25(OH)D <20 ng/ml) critically ill adults w...

Low protein diet (LPD) impairs body growth, decreases serum IGF1 and increases serum FGF21, two hepatokines influencing bone growth. Low calcium-phosphate diet (LCaPiD) increases serum calcitriol. We hypothesized that LPD effects on bone growth may differ according to calcium and phosphate intakes through the hormonal modulation of calcitriol, IGF1 and FGF21. One-month old rats were fed isocaloric diets containing 10 or 5% casein (10Prot, 5Prot), with 1.0% calcium and 0.8% pho...

Arterial stiffness or pulse wave velocity (PWV) is increasingly recognized as a strong predictor of future cardiovascular events and all cause mortality. Literature date indicate a relationship between vitamin D (25-OHD) deficiency and arterial stiffness in isolated systolic hypertension (ISH), but it is still unclear how 25-OHD deficiency may contribute to functional changes of the arterial wall in hypertensive patients. This study aimed to evaluate the relationships between ...

To further characterize the role of serotonin (5HT) in bone metabolism, Wistar-Zagreb rat model consisting of the high-5HT and low-5HT subline with different platelet 5HT content and transporter (5HTT) activity has been used.Primary osteoclasts from the high-5HT subline had an increased expression of 5HTT, 5HT–2A receptor, Trap and cathepsin K, while osteoblasts showed no difference in the expression of 5HT elements or osteoblastic markers. However,...

TSH exerts both antiresorptive and anabolic effects on bone remodeling in aged ovariectomized rats and TSH−/− mice, supported by clinical results demonstrating that low TSH level is associated with increased bone loss. To further explore the effect of TSH on bone metabolism we here introduced a rat model with removed thyroid and parathyroid glands to obtain low serum concentrations of thyroid and parathyroid hormone, calcitonin and 1,25(OH)2D<...

Vitamin D and its metabolites are bound to vitamin D binding protein (DBP) in the circulation. Only a small proportion is in unbound, free form. According to the ‘free-hormone-hypothesis’ only the free form is biologically active. DBP is a polymorphic protein and different variants of the protein differ in their ability to bind vitamin D. This may have an impact on the amount of free and bioavailable (free+albumin-bound) 25-hydroxyvitamin D (25(OH)D) in the circulati...

The purpose of the present study is to examine the relationship between the formation and composition of incremental lines in tooth dentin and the role of melatonin through histological and analytical studies. In this experiment, 5, 6 and 7 day old SD rats were used. These rats were divided into three groups: i) a control group (0.5% alcohol content drinking water); ii) a low concentration group (0.5% alcohol+20 μg/ml melatonin content drinking water); and iii) a high con...

1,25-Dihydroxyvitamin D (1,25D) is one of the major regulators of calcium metabolism. Due to its lipophilic nature and low circulating concentration, the measurement of 1,25D concentration levels has been labour intensive and technique dependent in addition to multiple equipments required for the sample purification procedure. We reported the results of soon to be commercialised fully on-board IDS-iSYS 1,25 VitDXp assay.IDS-iSYS 1,25 VitD...

Many reports have proposed significant role of vitamin D on immune mediated disease. This study analyzed lymphocyte subsets according to serum 25(OH) vitamin D levels in postmenopausal women to determine the potential effect of vitamin D on immune-mediated disease.On a prospective observational basis, we enrolled 31 postmenopausal women who underwent health checkup in our hospital. Peripheral blood drawn for the estimation of total T, B cell, NK cell cou...

Introduction: Atypical markers will provide interesting information in order to assess the bone metabolism. Serotonin has a dual action related to the bone and its serum level is the easiest to use in daily clinical practice also the exact value is not very well described up to this moment.Aim: We correlate to serum levels of serotonin with different results of clinical bone health evaluation in menopausal women.Materials and metho...

Objectives: The aim of this study was to determine the relationship between 25-hydroxyvitamin D (25(OH) D) level and blood pressure (BP) in Saudi women and to assess the effect of BMI, as a measure of adiposity, on this relationship.Methods: Three-hundred and three apparently healthy Saudi women (20–40 years old) were randomly selected for this cross-sectional study. All women signed an informed consent and the study was approved by the Ethical Comm...

PTH replacement therapy in hypoparathyroidism (hypoPT) has become more accepted after proving successful in several clinical studies. Intact PTH (PTH1–84) was in 2012 withdrawn, leaving teriparatide (PTH1–34) the only therapeutic option available.All patients with postoperative HypoPT who changed medication from PTH1–84 (100 μg) to PTH1–34 (20 μg), after at least 12 months of conve...

Introduction: Myostatin (growth differentiation factor 8, GDF-8) has an important role in the regulation of muscle mass, and mice lacking the myostatin gene show a generalized increase in bone density and strength. Type 2 diabetes subjects have an increased risk of fragility fractures despite of higher bone mass. Taking into account the myostatin influence in bone strength a better understanding of myostatin actions in type 2 diabetes is of interest.Obje...

The aim of the study was to evaluate time-related changes in serum concentration of bone tissue metabolism markers in Polish Large White male pigs. At birth, the piglets were divided into four groups. The first control group (n=7) received physiological saline i.m. (placebo). The second group (NanoCa group; n=7) were administered p.o. with nanopartical calcium (Ace Nano Calcium, NanoTechWorld, Pohang, Korea). The third group (Dex group; n=7) received...

There is the question, if routine screening of hypercalcemia and hypovitaminosis D in the whole Czech population may be considered meaningful and economical.Primary hyperparathyroidism is a frequent cause of hypercalcemia. At our clinic we surgically treat 180 patients diagnosed for primary hyperparathyroidism on average per year. In the sample we detect 24% rate of ectopic gland localization. Such ectopic localization complicates effective surgery, stre...

Objective: In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate zoledronate (Zln) inhibits lactation induced bone loss during lactation. In addition, to study if Zln interferes with recovery of bone mass after lactation has ceased.Materials and methods: 70 NMRI mice were divided into the following groups:...

Purpose: In X-linked hypophosphatemia (XLH), elevated serum FGF23 causes low serum phosphorus (Pi) and inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH)2D) levels. We report safety, tolerability and biochemistry markers following single ascending dose administration of KRN23 in adults with XLH.Methods: 38 XLH subjects with baseline FGF23≥30 pg/ml were randomized to receive single doses of KRN23 (K) or placebo (P) either (0.003&#15...

Purpose: In X-linked hypophosphatemia (XLH), elevated serum FGF23 causes low serum phosphorus (Pi) and inappropriately normal 125-dihydroxyvitamin D (125(OH)2D) levels. We report PK and PD of KRN23 following single ascending dose administration in adults with XLH.Methods: 38 XLH patients with baseline FGF23≥30 pg/ml were randomized to receive a single dose of KRN23 (K) or placebo (P) either i.v. (0.003–0.3 mg/kg) or s.c. (0.1–1...

Hypoparathyroidism results in low bone turnover and increased bone mineral density (BMD). Replacing deficient PTH with rhPTH(1–84) has the potential to correct these skeletal abnormalities. To investigate the effect of rhPTH(1–84) on BMD and bone turnover markers (BTMs), data from two studies were assessed.REPLACE, a double-blind, multicenter, placebo-controlled study, randomized 134 patients with hypoparathyroidism to receive once-daily rhPTH(...