Research

Cell and molecular biology

Influence of lathyrogenes on the function and development of osteoblasts

Lathyrogenes are substances which inhibt lysyloxidase which in turn is essential for collagen cross-linking (inter-molecular bonding). In this scientic focus, we study the influence of lathyrogens on the development and function of the osteoblasts which are forming this matrix or interact with it.

Effect of cell-cell-interaction on differentiation and gene-expression of osteoblasts

Cadherines and catenines are most important for cell contact, in particular ß-catenin which plays an important role for wnt-signaling. An essential aspect in this context is that during the development of tumor metastasis cell contact might get lost. For instance, tumors of the prostate (an epithelial tissue) can loose their contact to the tissue by deactivation of the epithelial E-cadherin.

Development of artificial tissue which can be resorbed and which enhances osteoblast growth and differentiation

At the Technical University of Vienna, new synthetic materials have been developed based on vinylester. At the LBIO, we test the biocompatibility of these new materials for their application in bone replacement materials.

Topographical influence of the bone surface on the differentiation and resorption ability of the osteoclasts

Osteoclasts are resorbing bone material thus are actively involved in bone remodelling process. The stimuli which are responsible for the activity of the osteoclast at the specific sites at the bone surface are unknown so far. We test if topographical features (such as cracks) are able to attract these cells and enhance their activity.

Bone structure/mechanics/mineral/organic matrix

Bone Fragility and Treatment

One focus is to get more insights into pathophysiological mechanisms leading to bone structural/material changes in diseases such as osteoporosis, diabetes…. Further we study how treatment acts on bone material properties creating the basis for future therapy options. A second focus was set on the bone material characteristics in rare bone diseases in which bone biopsy analysis is important for characterization of the bone phenotype and for treatment options.

Mineralization of osteoid and bone matrix

The basic mechanisms of the mineralization of the newly formed bone matrix (including the nucleation and growth of the mineral crystallites) are still to be elucidated. In general, two processes are involved in the mineralization of the bone matrix, including a primary rapid accumulation of mineral within the organic matrix and subsequently, a slower mineralization process. Nevertheless, it is unknown which proteins trigger this processes, how nucleation and growth of the crystallites occur in healthy bone and how the processes are altered in diseased bone.

Genetic determinants of bone material quality

Analysis of the bone material characteristics in human genetic diseases and/or in transgenic or knockout animal models provide to study the relationship between genetic mutations and their effect on the bone structure and material. One focus at the LBIO was set on bone from patients with osteogenesis imperfecta and on animal models of this disease. We have studied bone material from all clinical forms of osteogenesis imperfecta and recently have begun to characterize the bone material phenotyp of newly described forms of this disease.

Bone growth, development and ageing

During the development from the foetus to the adult individual, bone material is adapting to respective mechanical demands by structural and material changes. The investigation of these changes in the growing skeleton is the basis for the diagnosis of pathological deviations from normal development. Further research issues focus on fracture healing processes, detection of typical bone changes during development of osteoarthritis, and recently, the characterization of the bone material near to the osteocytes was introduced as a new scientific topic.

Micromechanics

As bone is a hierachically structured organ, mechanical properties arise from the combination of different hierarchical levels. We established a micromechanical testing device in order to get information on the bone material independent of structure and architecture of the bone.

Computed modeling and computer simulation

Using computed modeling (cooperation with the Max Planck Institute of Colloids and Interfaces) theoretical BMDD curves can be generated at different theoretical bone turnover situations (in particular non-stationary situations) or altered kinetics of mineralization which help to understand the experimentally observed BMDD.

Technical development

One of our strenghts at the LBIO is the combination of different techniques for the spatially resolved characterization of bone material. At present scanning acoustic microscopy and its combination with other techniques is established.

Clinical osteology

Idiopathic osteoporosis

Recently, a new scientific focus was set on the evaluation of the bone material in idiopathic osteoporosis. A clinical study of male osteoporosis was initiated at the LBIO in cooperation with the St. Vincent Hospital, Vienna. Clinical and biochemical characteristics will be studied and bone biopsy samples will be obtained from the patients.

Secondary prevention of osteoporotic fractures – an interdisciplinary ongoing project

The program started in 2005 and aims the development and testing of an interdisciplinary cooperation of diagnosis and therapy planning between the trauma surgery ward, the osteoporosis section of the internal ward, and GPs. Our reason for continuing the program is the necessity of still rising awareness for osteoporosis care in trauma surgeons and the high adherence to osteoporosis medication in patients enrolled in the program.

Rare skeletal disorders

An important part of our clinical work is the characterization of the phenotype of patients with skeletal dysplasias and various forms of congenital malformations in close collaboration with Prof. Franz E. Grill (Speising Orthopaedic Hospital – Pediatric Dept., Vienna, Austria) and Assoc.Prof. R. Ganger.

A Targeted screeing approach in orthopaedic surgery units to identify clinically symptomatic hereditary hemochromatosis patients

The frequency of iron overload in patients under the age of 70 years undergoing elective hip joint replacement surgery is measured. It is of interest whether a targeted screening approach in a high-risk population can identify clinically manifest HH patients before life-threatening liver involvement occurs.

Identification of gene polymorphisms associated with hip osteoarthritis

The causes of severe hip osteoarthritis necessitating joint replacement surgery are yet poorly understood. Aside age, female gender, diabetes and overweight, only few genetic markers for the susceptibility to hip OA are known.