Searchable abstracts of presentations at key conferences on calcified tissues

ba0002oc12 | Biology | ICCBH2013

Improvement of collagen synthesis in fibroblasts of Brtl model for osteogenesis imperfecta following lentiviral-shRNA-mediated down-expression of mutant Col1a1 allele

Trichet Valerie , Rousseau Julie , Gioia Roberta , Layrolle Pierre , Heymann Dominique , Rossi Antonio , Marini Joan , Forlino Antonella

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="...

ba0002oc22 | Miscellaneous | ICCBH2013

Prolidase deficient mice are osteoporotic in early life

Foster Sarah , Grabowski Peter , Gallagher Orla , Besio Roberta , Rossi Antonio , Bishop Nick , Forlino Antonella

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 ...

ba0005p444 | Other diseases of bone and mineral metabolism | ECTS2016

Deep characterization of a zebrafish model for dominant osteogenesis imperfecta

Tonelli Francesca , Gioia Roberta , Biggiogera Marco , Fisher Shannon , Leikin Sergey , Schinke Thorsten , Rossi Antonio , Forlino Antonella

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 ...

ba0005p216 | Chondrocytes and cartilage | ECTS2016

The role of CANT1 in skeletal development with a mouse model of Desbuquois dysplasia type 1

Monti Luca , Costantini Rossella , Paganini Chiara , Lecci Silvia , Maruelli Silvia , Biggiogera Marco , Cormier-Daire Valerie , Forlino Antonella , Rossi Antonio

Desbuquois dysplasia (DBQD) is a rare recessive chondrodysplasia, characterized by growth retardation, multiple dislocations and advanced carpal ossification. Two forms of DBQD have been described on the basis of the presence (type 1) or absence (type 2) of characteristic hand anomalies. DBQD type 1 is caused by mutations in the Calcium-Activated Nucleotidase 1 gene (CANT1), while DBQD type 2 is caused by mutations in the xylosiltransferase 1 gene.CANT1 ...

ba0006is03 | (1) (1) | ICCBH2017

Bone cells in health and disease

Besio Roberta , Gioia Roberta , Tonelli Francesca , Ceppi Ilaria , Leoni Laura , Atta Linda Ofori , Rossi Antonio , Forlino Antonella

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...

ba0007p37 | (1) | ICCBH2019

Generation of osteogenesis imperfecta type XIV zebrafish models

Leoni Laura , Tonelli Francesca , Cotti Silvia , Giannini Gabriella , Daponte Valentina , Gioia Roberta , Besio Roberta , Garibaldi Nadia , Rossi Antonio , Forlino Antonella

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 ...

ba0007p37 | (1) | IMPE2023

Generation of osteogenesis imperfecta type XIV zebrafish models

Leoni Laura , Tonelli Francesca , Cotti Silvia , Giannini Gabriella , Daponte Valentina , Gioia Roberta , Besio Roberta , Garibaldi Nadia , Rossi Antonio , Forlino Antonella

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 ...

ba0004oc12 | (1) | ICCBH2015

A zebrafish osteogenesis imperfecta model: a new tool to develop novel pharmacological treatments

Gioia Roberta , Tonelli Francesca , Carra Silvia , Cotelli Franco , Bianchi Laura , Gagliardi Assunta , Bini Luca , Biggiogera Marco , Leikin Sergey , Fisher Shannon , Rossi Antonio , Tenni Ruggero , Forlino Antonella

Objectives: Osteogenesis imperfecta (OI) is a bone disease mainly caused by collagen type I mutations and characterized by bone fragility. No definitive cure is available and the search for novel treatments is necessary. The small teleost D. rerio is particularly appealing for drug screening approaches. A zebrafish OI model (Chihuahua) carrying in heterozygosis the G574D substitution in the α1 chain of collagen type I is available. To use this model for ...

ba0007oc19 | (1) | ICCBH2019

Altered 3 hydroxylation complex in bone homeostasis

Tonelli Francesca , Leoni Laura , Cotti Silvia , Giannini Gabriella , Daponte Valentina , Gioia Roberta , Fiedler Imke , Besio Roberta , Rossi Antonio , Busse Bjorn , Witten Eckhard , Forlino Antonella

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 ...

ba0007oc19 | (1) | IMPE2023

Altered 3 hydroxylation complex in bone homeostasis

Tonelli Francesca , Leoni Laura , Cotti Silvia , Giannini Gabriella , Daponte Valentina , Gioia Roberta , Fiedler Imke , Besio Roberta , Rossi Antonio , Busse Bjorn , Witten Eckhard , Forlino Antonella

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 ...