Genetics of Bone Formation and Bone Density
In humans aging is invariably accompanied by changes in skin and bone. While age-related skin wrinkling is rather a cosmetic problem, age-related bone loss results in a increased susceptibility to fractures and thus a significant disease burden. To elucidate the molecular processes that govern aging in these tissues, we studied a group of recessively inherited diseases collectively characterized by the combination of wrinkly skin and osteoporotic bone. Over the last years we have been able to identify disease causing mutations in three different genes, two of which are involved in the Golgi networkand mitochondria.
The bone mass of our body is regulated via complex feedback loops, loss of bone results in osteoporosis, a condition that is invariably associated with ageing and that results in an increased susceptibility to fractures. To elucidate the molecular processes that govern osteoporosis and ageing in bone, we are studying the genetic causes of abnormal bone density. We have been able to identify disease-causing mutations in several different genes (GORAB, ATP6V0A2, PYCR1, WNT1), two of which are involved in the Golgi network. Our findings provide new insights into the molecular mechanisms of skin ageing and osteoporosis. Increased susceptibility to apoptosis and/or senescence appears to be an important trigger for age-related changes in skin and bone. Current studies focus on the identification of novel disease genes and the characterization of pathogenic mechanisms in osteoporosis, in particular, related to senescence. Studies are being carried out to determine the prevalence of mutations in patients with early-onset osteoporosis.