Bone Abstracts

Bone is a complex tissue constituted by a mineral phase, hydroxyapatite, and an organic phase, mainly represented by collagen type I. Specialized cells are responsible for bone formation and remodeling. Osteoblasts represent the bone forming cells, osteocyte are the orchestrator of bone remodeling through regulation of the other bone cells activity, by functioning as endocrine cells and by acting as mechanosensor, and osteoclasts, the bone resorbing cells. Mesenchymal osteopro...

Objectives: Osteogenesis Imperfecta (OI) type XIV is a recessive OI form characterized by bone fragility, multiple fractures and growth retardation. It is caused by mutation in TMEM38B gene encoding the endoplasmic reticulum (ER) channel TRIC-B. This channel allows the transport of K+ across the ER membrane modulating Ca2+ flux. Defective ER Ca2+ impaires collagen type I synthesis, likely affecting the activity of ER enzymes involved in its post translational modification. To ...

Objectives: Different versions of the Childhood Health Questionnaire (CHAQ) have been used in Paediatric Rheumatology since 1994 to establish levels of functional disability. To date, use of the CHAQ has not been reported in Osteogenesis Imperfecta (OI). The aim of this study was to establish if disability scores generated from a modified CHAQ (MCHAQ) correlate with OI severity.Methods: The MCHAQ was developed to reflect the specific needs of children wi...

Objectives: Osteogenesis imperfecta (OI) is a heritable disorder characterized by bone deformity and skeletal fragility. Cartilage associated protein (CRTAP), proline 3-Hydroxylase 1 (P3H1) and Cyclophylin B (PPIB) are components of the endoplasmic reticulum (ER)-resident complex involved in the 3-hydroxylation of specific proline residues in collagen type I α chains. Mutations in these proteins are responsible for recessive OI type VII, VIII and IX, respectively. Murine ...

Objectives: The Brtl mouse, a unique model for the autosomal dominant forms of osteogenesis imperfecta was used to prove the feasibility of a lentiviral-shRNA-based strategy to improve collagen quality by targeting the mutant Col1a1 allele at the point mutation responsible for the causative substitution Gly349Cys. The ability to specifically suppress the mutant allele should convert the moderate Brtl outcome to the mild one caused by quantitative defect.<p class="...

Background: Proline and hydroxyproline account for ~25% of aminoacids in collagen., Prolidase (peptidase D (EC 3.4.14.9)), cleaves iminodipeptides with a C-terminal proline or hydroxyproline, playing a major role in collagen catabolism. Mice with prolidase deficiency (PD) present with varied phenotypes including reduced size compared to wild-type littermates. We measured structural and mechanical properties of bones in PD mice.Methods: Whole femurs from ...

Dominant osteogenesis imperfecta (OI) is a bone disease mainly caused by collagen type I mutations and characterized by bone fragility and growth delay. Nowadays no definitive cure is available. A zebrafish OI model (Chihuahua) carrying an heterozygous G574D substitution in the α1 chain of collagen type I was generated by ENU mutagenesis and is available in our laboratory. Control (WT) and mutant (Chi+/−) fish growth was followed up from day 1 post fertilization to ...

After many years of study, researchers show that obesity can harm the bones. It is not known whether the increased fat mass can accelerate the process of bone loss. The aim of this study was to evaluate whether high-fat diet accelerates the process of bone loss in ovariectomized rats. This study was approved by the Ethics Committee of our Institution (188/2013). 40 female wistars rats with body mass of 60 g were used in this study. They were equally divided into four experimen...

Bone tissue homeostasis requires the coordinated activity of osteoblasts, the bone forming cells, of osteoclasts, the bone resorbing cells, and of osteocytes, generally referred as the bone mechano-sensors. In this contest, osteoblasts are the mesenchymal cells secreting the extracellular matrix components on which hydroxyapatite crystals are then deposited. The most abundant protein of this organic matrix is type I collagen, a heterotrimeric secretory protein, synthesized as ...

Objectives: Bisphosphonates are frequently used in children with skeletal disorders, however optimal dosing and regimens are unknown. Early treatment focused on pamidronate (PAM), a second-generation formulation, however use of zoledronate (ZOL), a more potent third-generation bisphosphonate, has recently increased due to shorter and less frequent infusions. The objective of this study is to compare short-term safety of ZOL and PAM in a pediatric population.<p class="abste...