Osteoporosis is a disease in which the bones become weak and brittle, increasing the risk of fracture. Bone is a living tissue that constantly regenerates and the body maintains a balance between the creation of new bone cells and the removal of old cells. As we age, the rate at which the new bone replaces the old or damaged bone slows and the bone density gradually decreases. But if this frequency slows too much, it can lead to osteoporosis. Osteoporosis is a major public health problem and is more common in women than in men. Estimates suggest that around 1 in 3 women and 1 in 5 men over age 50 suffer from bone fractures due to osteoporosis. In women over the age of 45, the disease represents more days spent in hospital than diabetes, heart attack and breast cancer. In the United States, osteopenia and osteoporosis are believed to affect over half (55%) of people aged 50 and over. The progenitor cells are immature cells that are in reserve until they receive genetic instructions from the transcription factors, that indicate to them what type of cell it must become. In the case of bone tissue, progenitor cells are mesenchymal stem cells of the bone marrow.
Depending on the instructions they receive, mesenchymal stem cells can mature into: bone-producing cells called osteoblasts; cells producing cartilage or chondrocytes; and adipocytes or fat cells. Until now it was not clear what controlled the direction of maturity of the progenitor cells, so as to maintain the delicate balance or homeostasis of bone formation. In the journal PNAS, scientists at the University of Alabama in Birmingham and Zhejiang University in China explain how a nuclear protein called CBF-beta is important for controlling the speed at which new bone cells replace old ones. When they studied the transcription factors that control the direction of maturity, the team found that a protein called the beta-binding subunit of the core binding factor (CBF-beta) was vital for the change of targets between bone-producing cells and fat cells. To undertake the study, the team engineered three groups of mice by eliminating CBF-beta at three different stages in the maturation of progenitor cells. The team found that all three groups of mice developed severe osteoporosis, having accumulated fat cells in their bone marrow.
The pattern was similar to that observed in age-related bone loss. They also found an increase in the expression of fat cell genes in bone marrow mesenchymal stem cells, and in bone cells in the skulls of mice lacking CBF-beta. When CBF-beta activates a signal within a cell type known as Wnt10b / beta-catenin, it blocks the expression of the gene that directs progenitor cells to mature into fat cells. The team also found that CBF-beta drives progenitor cells to become bone-producing cells through another type of signal sent to neighboring cells: the Wnt paracrine pathway. The researchers hope that their mapping will improve the understanding of the role that CBF-beta plays in maintaining bone, especially with age. The investigations of this study will fill an important gap in knowledge and could facilitate the development of new therapies for bone loss, which are devoid of negative side effects from current osteoporosis therapy.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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