Bone Abstracts

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...

Background: Hypophosphatasia (HPP) is caused by inactivating mutations in the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). HPP is variable in clinical manifestations and prognosis, and is generally classified into six subtypes: perinatal lethal, perinatal benign (prenatal benign), infantile, childhood, adult, and odonto HPP. Although genetic test is broadly used for diagnosis of HPP, the genotype-phenotype relationship still remains unclear.<p class...

Backgrounds: Osteogenesis imperfecta (OI) is an inherited bone disease caused by qualitative or quantitative defects in type I collagen, and is characterized by bone fragility and ligamentous laxity. Spine disorder is an important symptom in children with OI, and respiratory difficulties secondary to spinal disorder were identified as a main cause of death in these patients. Reduced fracture rates and prevention of long-bone deformities have been reported in children with OI w...

Objectives: Osteogenesis imperfecta (OI) is a relatively common skeletal dysplasia characterized by bone fragility, mainly resulting from mutations in the COL1A1 and COL1A2 genes. Phenotype–genotype correlation is not fully uncovered in OI. Additionally, more than ten genes have been found to be responsible for OI. In the current study, we determine mutations in patients with OI using a targeted exome sequencing and examine a phenotype–genotype correlation.<p cla...

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: 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...

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...