An -Ethyl--Nitrosourea (ENU) Mutagenized Mouse Model for Autosomal Dominant Nonsyndromic Kyphoscoliosis Due to Vertebral Fusion.

Kyphosis and scoliosis are common spinal disorders that occur as part of complex syndromes or as nonsyndromic, idiopathic diseases. Familial and twin studies implicate genetic involvement, although the causative genes for idiopathic kyphoscoliosis remain to be identified. To facilitate these studies, we investigated progeny of mice treated with the chemical mutagen -ethyl--nitrosourea (ENU) and assessed them for morphological and radiographic abnormalities.

Switch from sexual to parthenogenetic reproduction in a zebra shark.

Parthenogenesis is a natural form of asexual reproduction in which embryos develop in the absence of fertilisation. Most commonly found in plants and invertebrate organisms, an increasing number of vertebrate species have recently been reported employing this reproductive strategy. Here we use DNA genotyping to report the first demonstration of an intra-individual switch from sexual to parthenogenetic reproduction in a shark species, the zebra shark Stegostoma fasciatum.

The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21WAF1/CIP1 in 143B Osteosarcoma Cell Growth Arrest.

Mutations of the forkhead transcription factor FOXP2 gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from Foxp2 disruption have been described. However, molecular functions of FOXP2 are not completely understood. Here we report a requirement for FOXP2 in growth arrest of the osteosarcoma cell line 143B.

Bone healing response to a synthetic calcium sulfate/β-tricalcium phosphate graft material in a sheep vertebral body defect model.

The introduction of a material able to promote osteogenesis and remodelling activity in a clinically relevant time frame in vertebroplasty and kyphoplasty procedures may have patient benefit. We report the in-vivo performance of a biphasic synthetic bone graft material (Genex Paste, Biocomposites, UK) [test material], composed of calcium sulfate and β-tricalcium phosphate, implanted into a sheep vertebral defect model. Cavities drilled into 4 adjacent vertebrae (L2 to L5) of 24 skeletally mature sheep were; (1) filled with the test material; (2) filled with commercially available polymethylmethacrylate [PMMA] cement; (3) remained empty [sham].

Prdm5 regulates collagen gene transcription by association with RNA polymerase II in developing bone.

PRDM family members are transcriptional regulators involved in tissue specific differentiation. PRDM5 has been reported to predominantly repress transcription, but a characterization of its molecular functions in a relevant biological context is lacking. We demonstrate here that Prdm5 is highly expressed in developing bones; and, by genome-wide mapping of Prdm5 occupancy in pre-osteoblastic cells, we uncover a novel and unique role for Prdm5 in targeting all mouse collagen genes as well as several SLRP proteoglycan genes.

Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis.

Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease primarily involving the synovium. Evidence in recent years has suggested that the bone marrow (BM) may be involved, and may even be the initiating site of the disease. Abnormalities in haemopoietic stem cells' (HSC) survival, proliferation and aging have been described in patients affected by RA and ascribed to abnormal support by the BM microenvironment.

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo.

Cancers that grow in bone, such as myeloma and breast cancer metastases, cause devastating osteolytic bone destruction. These cancers hijack bone remodeling by stimulating osteoclastic bone resorption and suppressing bone formation. Currently, treatment is targeted primarily at blocking bone resorption, but this approach has achieved only limited success.

The effect of tibial lengthening on immature articular cartilage of the ankle joint.

Is the articular cartilage of the immature ankle joint damaged by tibial lengthening? Sixteen immature rabbits underwent a 30% diaphyseal lengthening by tibial callotasis. Damage was assessed by scanning electronic microscopy and histomorphometry at the completion of distraction and after an additional 5 weeks. Despite joint contracture, little damage in the articular cartilage was observed in contrast to the knee joint.

Bortezomib alone or in combination with the histone deacetylase inhibitor JNJ-26481585: effect on myeloma bone disease in the 5T2MM murine model of myeloma.

The proteasome inhibitor bortezomib (Velcade) is currently approved as second-line treatment of multiple myeloma (MM). MM-related bone disease is one of the most debilitating complications of MM. Besides supportive care with biphosphonates, which have proven efficacy in reducing and delaying skeletal-related events, there is no specific treatment of lytic bone lesions.

Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma.

Multiple myeloma (MM) is associated with the development of osteolytic bone disease, mediated by increased osteoclastic bone resorption and impaired osteoblastic bone formation. Dickkopf-1 (Dkk1), a soluble inhibitor of wingless/int (Wnt) signaling and osteoblastogenesis, is elevated in patients with MM and correlates with osteolytic bone disease. In this study, we investigated the effect of inhibiting Dkk1 on the development of osteolytic lesions in the 5T2MM murine model of myeloma.

Geranylgeranyl transferase type II inhibition prevents myeloma bone disease.

Geranylgeranyl transferase II (GGTase II) is an enzyme that plays a key role in the isoprenylation of proteins. 3-PEHPC, a novel GGTase II inhibitor, blocks bone resorption and induces myeloma cell apoptosis in vitro. Its effect on bone resorption and tumor growth in vivo is unknown.

The effect of tibial diaphyseal lengthening on the longitudinal growth of the tibia.

Limb lengthening by tibial callotasis is usually performed in the metaphysis but may cause growth inhibition. Is diaphyseal lengthening more advantageous? Sixteen immature rabbits underwent 30% diaphyseal lengthening by tibial callotasis. The tibial length was measured on radiographs at the end of the distraction period and after an additional 5 weeks.

A new xenograft model of myeloma bone disease demonstrating the efficacy of human mesenchymal stem cells expressing osteoprotegerin by lentiviral gene transfer.

We describe a new model of myeloma bone disease in which beta2m NOD/SCID mice injected with KMS-12-BM cells develop medullary disease after tail vein administration. Micro-computed tomography analysis demonstrated significant bone loss in the tibiae and vertebrae of diseased animals compared to controls, with loss of cortical bone (P<0.01), as well as trabecular bone volume, thickness and number (P<0.

Targeting the IGF-1R using picropodophyllin in the therapeutical 5T2MM mouse model of multiple myeloma: beneficial effects on tumor growth, angiogenesis, bone disease and survival.

During the last decade, a central role for insulin-like growth factor 1 (IGF-1) in the pathophysiology of multiple myeloma (MM) has been well established. IGF-I provided by the tumor-microenvironment interaction may directly and indirectly facilitate the migration, survival and expansion of the MM cells in the bone marrow (BM). The inhibition of the IGF-1R-mediated signaling pathway has recently been suggested to be a possible new therapeutic principle in MM.

Inhibition of p38alpha mitogen-activated protein kinase prevents the development of osteolytic bone disease, reduces tumor burden, and increases survival in murine models of multiple myeloma.

The bone microenvironment plays a critical role in supporting the growth and survival of multiple myeloma as well as in the development of osteolytic bone disease. Signaling through p38alpha mitogen-activated protein kinase (MAPK) mediates synthesis of multiple myeloma cell growth factors, and its inhibition reduces proliferation in vitro. However, it is unclear whether targeting p38alpha MAPK prevents multiple myeloma growth and the development of bone disease in vivo.

The effect of GSM and TETRA mobile handset signals on blood pressure, catechol levels and heart rate variability.

An acute rise in blood pressure has been reported in normal volunteers during exposure to signals from a mobile phone handset. To investigate this finding further we carried out a double blind study in 120 healthy volunteers (43 men, 77 women) in whom we measured mean arterial pressure (MAP) during each of six exposure sessions. At each session subjects were exposed to one of six different radio frequency signals simulating both GSM and TETRA handsets in different transmission modes.

Role of CCR1 and CCR5 in homing and growth of multiple myeloma and in the development of osteolytic lesions: a study in the 5TMM model.

Multiple myeloma (MM) is a plasma cell malignancy, characterized by the localization of the MM cells in the bone marrow (BM), where they proliferate and induce osteolysis. The MM cells first need to home or migrate to the BM to receive necessary survival signals. In this work, we studied the role of CCR1 and CCR5, two known chemokine receptors, in both chemotaxis and osteolysis in the experimental 5TMM mouse model.

The effect of induced biphasic pulsed currents on re-epithelialization of a novel wound healing model.

The coordinated migration of keratinocytes is crucial to cutaneous wound healing; failure of keratinocytes to migrate into a wound can lead to chronic non-healing wounds. Keratinocyte migration can be influenced by applied electrical fields. Our aim was to investigate whether keratinocyte migration could be accelerated by applying an induced biphasic pulsed electrical field.

The effect of tibial lengthening on immature articular cartilage of the knee joint.

Objective: To investigate the acute response of immature articular cartilage, in the distraction and consolidation phases, to 30% tibial lengthening.

Design: Sixteen immature New Zealand white rabbits underwent diaphyseal lengthening of the left tibia by callotasis at a distraction rate of 0.4mm twice daily.

Radiographic classification of osteogenesis during bone distraction.

Successful limb lengthening requires serial radiological evaluation of the progression of healing of the regenerate bone. However, there is no radiographic classification system that shows how the regenerate should progress during treatment in adults. The study aimed to address this need.

Effect of 900 MHz electromagnetic fields on nonthermal induction of heat-shock proteins in human leukocytes.

Despite many studies, the evidence as to whether radiofrequency fields are detrimental to health remains controversial, and the debate continues. Cells respond to some abnormal physiological conditions by producing cytoprotective heat-shock (or stress) proteins. The aim of this study was to determine whether exposure to mobile phone-type radiation causes a nonthermal stress response in human leukocytes.

Distraction-resisting force during tibial diaphyseal lengthening and consolidation--a study on a rabbit model.

Background: Distraction-resisting force is generated in the soft tissues and callus during limb lengthening. Monitoring this force may offer a method of studying the behaviour of soft tissue and detecting the distraction osteogenesis related problems, and help to prevent complications. Changes in the post distraction period have not been previously investigated and there are no reports on the contribution of gastrocnemius to the distraction-resisting force.

Knee joint reaction force during tibial diaphyseal lengthening: a study on a rabbit model.

The in vivo passive knee joint reaction force was measured in a rabbit model of tibial diaphyseal lengthening. This was based on the assumption that limb lengthening creates soft tissue tension that compresses the joint surface and generates the joint contact force. A measurement method was developed that involved the distraction of the joint and the determination of the distraction force that just separates the joint surfaces.

Effect of 50 Hz electromagnetic fields on the induction of heat-shock protein gene expression in human leukocytes.

Although evidence is controversial, exposure to environmental power-frequency magnetic fields is of public concern. Cells respond to some abnormal physiological conditions by producing cytoprotective heat-shock (or stress) proteins. In this study, we determined whether exposure to power-frequency magnetic fields in the range 0-100 microT rms either alone or concomitant with mild heating induced heat-shock protein gene expression in human leukocytes, and we compared this response to that induced by heat alone.