PPAR-g Regulatory Networks in Bone Metabolism And Mineralization

Abstract

Bone is a highly dynamic tissue that is permanently remodeled as an intrinsic mechanism to regenerate bone during life, to accomplish longitudinal growth, and to generate new bone during fracture repair. As bone formation must match closely the amount of bone that is resorbed at each site, bone remodeling is controlled by the coupled actions of osteoclasts and osteoblasts. Osteoblasts control the formation and activity of osteoclasts that are responsible for the initiation and execution of resorption at remodeling sites. The bone resorbed by osteoclasts is replaced through the differentiation and activity of osteoblasts. This coupling of the two processes is essential for bone balance. Due to age, sex hormone status, cancer and a variety of diseases associated with an activation of the immune system, the balance between bone resorption and formation can be shifted leading to local or systemic bone loss that ultimately results in osteoporosis. Osteoporosis is a prevalent skeletal disorder in the elderly that is characterized by impaired bone strength and increased fracture risk. It is associated with reduced life quality and increased mortality. On the other hand, excessive bone formation can give rise to sclerosing bone disorders that include many rare and often hereditary osteochondrodysplasias (e.g. osteopetrosis, Van Buchem disease and sclerosteosis), but can also be caused by a variety of dietary, metabolic, endocrine, hematologic, infectious or neoplastic disorders.