Osteoporosis, an age-related bone loss disease in which bones become weak and brittle, increasing the risk of fractures. Bone is a living tissue that is constantly regenerating, and the body maintains a balance called homeostasis between the creation of new bone cells and the removal of old cells.
Osteoporosis is a big global health problem, and more common in women than in men. Around 1 in 3 women and 1 in 5 men over the age of 50 experience bone fractures due to osteoporosis. In the United States, low bone mass and osteoporosis thought to affect over 55% of people aged 50 and older.
Researchers mapped a cell mechanism, called Cbf-beta, plays a key role in Osteoporosis. This mechanism, progenitor cells stop creating a bone-producing cells, and instead create fat cells. This mechanism can provide targets in the search for novel bone-loss therapeutics to treat human osteoporosis with minimal side-effects.
The rate at which new bone replaces old or damaged bone slows down and bone density gradually diminishes. But, if this rate slows too much, it can lead to osteoporosis.
Progenitor cells are immature cells that stand in reserve until they receive genetic instructions from transcription factors that tell them which type of cell to become. In the case of bone tissue, the progenitor cells are bone marrow “mesenchymal stem cells.”
Depending on the instructions they receive, the mesenchymal stem cells can mature into bone-producing cells called osteoblasts.
Until now not clear what controlling the direction of maturity of the progenitor cells to maintain the delicate equilibrium or homeostasis of bone formation.
The team found that a protein called core-binding factor subunit beta (Cbf-beta), vital for switching destinations between bone-producing cell and fat cell.
Researchers engineered three groups of mice by deleting Cbf-beta at three different stages in the maturation of the progenitor cells.
The team found that all three groups of mice developed severe osteoporosis and accumulated fat cells in their bone marrow. The pattern similar to that seen in age-related bone loss.
They also found increased expression of fat cell genes in the progenitor cells. The bone marrow mesenchymal stem cells, and bone cells of the skulls of mice lacking Cbf-beta.
Further investigation showed that when Cbf-beta activates a signal inside a type of cell known as Wnt10b/beta-catenin. It blocks expression of the gene that directs the 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 Wnt signal sent to nearby cells.
Their results improve understanding of the role that Cbf-beta plays in maintaining bone, especially as we age.