Bone Abstracts

Eldecalcitol (ED-71; ELD), a 2β-hydroxypropyloxy derivative of 1α,25(OH)2D3, was approved to treat osteoporosis in Japan in 2011. The endothelial protective effect of vitamin D3 in osteoporosis is not clear. This study evaluated the endothelial protective effect of ELD in ovariectomized (OVX) rats.ELD (20 ng/kg) was orally administered five times a week for 4 weeks from 1 day after OVX surgery. Four weeks after surgery, flow-mediated dilation (...

Objectives: We have performed a novel cell therapy using culture-expanded bone marrow cells (BMC) and platelet rich plasma (PRP) during limb lengthening procedure since 2002. In the present study, we evaluated the efficacy of the cell therapy on new bone regenerates in patients with achondroplasia (ACH) and hypochondroplasia (HCH).Methods: The transplantation technique of BMC and PRP was described previously (Bone 40: 522–528, 2007). Inclusion crite...

ACH (achondroplasia) is one of the most common skeletal dysplasias with severe short stature caused by gain-of-function mutations in the FGFR3 gene. Foramen magnum stenosis is a serious neurological complication of ACH. Downregulation of the FGFR3 signaling is a radical therapeutic strategy for the disease. We previously demonstrated that meclozine, an over-the-counter drug for motion sickness, inhibited elevated FGFR3 signaling in chondrocytic cell lines. In the present study...

Background: Hypophosphatasia (HPP) is characterized by defective mineralization of bone and/or teeth in the presence of low serum alkaline phosphatase (ALP) activity and caused by mutations in the ALPL gene encoding tissue-nonspecific ALP. Odontohypophosphatasia (odonto HPP) is the mildest form of hypophosphatasia and characterized by dental complications without abnormalities of the skeleton system.Objectives: We aimed to investigate biochemical and gen...

Wnt signaling is a major regulator of bone metabolism. We recently reported that mutations in WNT1 gene in humans cause early onset osteoporosis and severe osteogenesis imperfecta. To identify the cellular source and the mechanisms causing these severe phenotypes we generated and analyzed global and conditional Wnt1 knockout mice.Heterozygous Wnt1+/− mice were viable and fertile but Wnt1−/− embryos were lost in ute...

Objectives: Endochondral ossification in the growth plate cartilage (GPC) plays a crucial role in the determination of the length and shape of long bones. Many skeletal dysplasias are caused by GPC dysfunction, associated with short stature. We have already reported that human iPS cell-derived cartilage (hiPSC-Cart), when implanted into the subcutaneous spaces of the SCID mice for 4 weeks, formed skeletal tissue like GPC. This model could also recapitulate the pathology of FGF...

Objective: Hypophosphatasia (HPP) is a rare, inherited metabolic disease characterized by bone mineralization defects and osteomalacia, as well as systemic manifestations, including seizures, respiratory insufficiency, muscle weakness, nephrocalcinosis, and pain. The biochemical hallmark of HPP is low serum alkaline phosphatase, resulting from loss-of-function mutations in the gene encoding tissue non-specific alkaline phosphatase. HPP presents a broad spectrum of disease seve...

Objectives: Limited data exist on growth parameters in children with hypophosphatasia (HPP), a rare metabolic disease characterized by impaired bone mineralization. We aimed to describe growth characteristics in untreated children with HPP enrolled in the Global HPP Patient Registry.Methods: Children (<18 years old) with a diagnosis of HPP who were not receiving enzyme replacement therapy with asfotase alfa at the time of evaluation were identified f...

Objectives: As osteoblasts mature, they acquire the expression of multiple molecules involved in phosphate metabolism, including dentin matrix protein 1 (DMP1) and fibroblast growth factor 23 (FGF23). This suggests that osteoblasts and osteocytes may sense and respond to alterations in the phosphate availability in their microenvironment. We previously reported that increased extracellular inorganic phosphate (Pi) triggered signal transduction in various cell types to alter ge...

Objectives: Osteogenesis Imperfecta (OI) is a heritable brittle bone disease mainly caused by mutation of COL1A1 or COL1A2. Treatment with bisphosphonate is not effective enough in patients with severe OI. 4-phenylbutyric acid (4-PBA) may become a new medicine, which was reported to ameliorate the phenotype of an OI zebrafish model. In the present study, we aimed to analyze the pathology of OI and the effects of 4-PBA on patient-derived fibroblasts and induced pluripotent stem...