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Bone Abstracts (2017) 6 IS03 | DOI: 10.1530/boneabs.6.IS03

Department of Molecular Medicine, University of Pavia, Pavia, Italy.

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 osteoprogenitors and hematopoietic osteoclast precursor cells need also to be considered as active players in bone homeostasis. The bone cellular compartment is a dynamic environment and the cell crosstalk is regulating its activity. Abnormality in bone cell function causes various human diseases. Osteogenesis imperfecta (OI), also known as brittle bone disease, is a heritable skeletal dysplasia characterized by bone fragility and deformity, frequent fractures and short stature. Classical OI is caused by dominant mutations in the collagen type I coding genes, COL1A1 and COL1A2, but also defects in other proteins involved in collagen type I synthesis, posttranslational modification, maturation and secretion as well as in osteoblasts differentiation had been more recently described as causative for the disease. The bone phenotype of OI patients was traditionally attributed to the presence of altered collagen type I in the bone extracellular matrix. More recently, it became clear that that for OI, as for other skeletal dysplasia, a cellular function impairment, due to mutant protein retention, may have an effect on patients’ outcome and could be a target for the disease treatment. By using the OI murine model Brtl and the OI zebrafish model Chihuahua, carrying a typical glycine substitution in one α1 chain of collagen type I we demonstrated that the severity of the disease could be modulated by a different ability of bone to cope with the stress caused by mutant collagen retained in the endoplasmic reticulum. Many evidences suggest that intracellular events contribute to the OI phenotype and cellular stress seems to be an appealing new pharmacological target for OI.

Fondazione Cariplo 2013-0612, Telethon GGP13098 and the European Community n. 602300, Care4brittlebones Project 0003, 2014.

Disclosure: The authors declared no competing interests.

Volume 6

8th International Conference on Children's Bone Health


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