Regulation of bone metabolism by systemic hormones, inflammatory mediators and neuropeptides. Preclinical and clinical studies.

Project description

Bone is continously remodeled by the concerted actions of bone resorbing osteoclasts and bone forming osteoblasts in restricted areas of the skeleton. In pathological conditions such as osteoporosis, increased number of osteoclasts and decreased activity of osteoblasts result in loss of bone and increased fracture risk. In inflammatory diseases such as periodontal disease and rheumatoid arthritis, increased expression of cytokines and kinins result in increased osteoclast formation and as a consequence local loss of bone surronding the teeth or in the joints. The present project aims to study mechanisms involved in regulation of osteoclast formation, osteoclast activity and ostoblastic bone formation by hormones and inflammatory mediators. The role in bone metabolism of signaling molecules in skeletal nerve fibers will be particularly addressed. The studies are performed mainly in cell- and organ cultures using cell- and molecular biology approaches, including assessments of gene expression by cDNA arrays, quantitative realtime PCR, FACS, Western blots, EMSA, transfection of cells with mutated promotors. Studies are also performed with mice with gene knockouts. Our hypothesis will also be evaluated in patients with emphasis on bone resorbing activitities in inflammatory exudates from patients with periodontitis or loosened prosthesis. We also will study the importance of genetic polymorphisms in periodontitis patients and the influence of osteoporosis on periodontal disease.