Bone Abstracts

Introduction: The matrilin-3 polymorphism T298M has been described to be associated with hand osteoarthritis in the carpometacarpal joint 1 (CMC1) and with spinal disc degeneration. In vitro studies revealed that expression levels, processing and secretion of matrilin-3 T298M were similar to the wt protein. Structural analysis indicated an impact on the formation of collagen II/IX/XI heterofibrils, whereas the binding to collagen was not affected. We have now generate...

COMP (Cartilage Oligomeric Matrix Protein) is a member of the thrombospondin family of extracellular matrix proteins and also referred to as thrombospondin-5. Mutations in COMP lead to chondrodysplasias. Here we studied COMP in zebrafish (Danio rerio) which is a powerful vertebrate model organism. In silico analysis revealed that only one COMP coding gene exists in zebrafish and that the domain structure of COMP is fully conserved. Inspection of gene locus and phyloge...

Biographical DetailsDr Frank Rauch obtained his MD degree from the Technical University of Munich, Germany, and trained as a pediatrician at the Children’s Hospital of Cologne University, Germany. Since 2001 Dr F Rauch has been a clinician-scientist at the Shriners Hospital for Children and is currently a Professor of Pediatrics at McGill University, Montreal, Canada. His clinical an...

Osteogenesis imperfecta (OI) is not only characterized by fragile bones but also impaired muscle mass and function. Inhibition of signaling through the activin receptor IIB has the potential to improve both muscle and bone mass. Here we investigated the effect of a soluble activin receptor IIB ligand, ACE-2494 (10 mg/kg twice a week), in 4-week old Col1a1Jrt/+ male mice, a model of severe dominant OI caused by a Col1a1 splice site mutation. Four weeks of treatment with ACE-249...

Muscle size and function are closely correlated with skeletal development. Examining the relationship between muscle and bone is thus of central interest in clinical bone research. Surprisingly, however, there is little information on how to evaluate the functional muscle-bone relationship in clinical studies. Many past studies on muscle–bone interaction seem to have analyzed muscle and bone measures that were convenient to collect but did not evaluate a specific model of...

Biographical DetailsFrank Rauch trained as a pediatrician at the Children’s Hospital of Cologne University, Germany, where he started working on pediatric bone disorders in Dr Schoenau’s laboratory. He then performed a research fellowship on metabolic bone disorders at the Shriners Hospital for Children, Montreal, Canada. Since 2001 he has been a clinician scientist at the Shrin...

Osteogenesis imperfecta (OI) is usually caused by dominant mutations affecting one of the two genes that code for two collagen type 1, but a recessive form of OI is present in 5–10% of individuals with a clinical diagnosis of OI. Most of the involved genes code for proteins that play a role in the processing of collagen type 1 protein (BMP1, CREB3L1, CRTAP, LEPRE1, P4HB, PPIB, FKBP10, SERPINF1, SERPINH1, PLOD2, SEC24D, and TMEM38B), or interfere with ost...

Pediatric bone health research is rapidly expanding. As many bone disorders in children are rare, the field benefits from the attention that rare disorders in general are currently receiving. Consequently, new approaches for treating bone diseases in children have been developed and are being studied in clinical trials. The treatment of hypophosphatasia with bone-targeted enzyme replacement therapy is one of the most advanced programs in this area. New studies on this approach...

Biographical DetailsFrank RauchFrank Rauch, MD, is a Professor of Pediatrics and clinician-scientist at the Shriners Hospital for Children and at McGill University. His clinical activities and research program concentrate on improving bone health in children, with a special focus on genetic conditions leading to fractures and on the role of the musc...

Arterial calcification is now considered as an actively regulated process resembling osteogenesis orchestrated by a number of systemic or constitutively expressed mediators. Genetic studies of rare inherited syndromes have identified key regulators of arterial calcification. Based on the pathogenic principles causing the diseases these can be classified into three groups:i) Disorders of an increased extracellular inorganic phosphate/inorganic pyrophospha...