Osteoporosis: Biology behind age-related bone loss revealed
In the journal PNAS, scientists from both the University of Alabama at Birmingham and Zhejiang University in China explain how a protein called Cbf-beta is important for controlling the rate at which new bone cells replace old ones.
Osteoporosis is a 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.
As we age, 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.
Osteoporosis is a big global 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 the age of 50 experience bone fractures due to osteoporosis.
In women over the age of 45, the disease accounts for more days spent in hospital than diabetes, heart attack, and breast cancer.
In the United States, low bone mass and osteoporosis are thought to affect over half (55 percent) of people aged 50 and older.
Progenitor cells
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; cartilage-producing cells, or chondrocytes; and adipocytes, or fat cells.
Until now, it was not clear what was controlling the direction of maturity of the progenitor cells so as to maintain the delicate equilibrium or homeostasis of bone formation.
When they investigated the transcription factors controlling the direction of maturity, the team found that a protein called core-binding factor subunit beta (Cbf-beta) was vital for switching destinations between bone-producing cell and fat cell.
Cbf-beta plays key role
The team found that all three groups of mice developed severe osteoporosis and accumulated fats cells in their bone marrow. The pattern was similar to that seen in age-related bone loss.
They also found increased expression of fat cell genes in the progenitor cells – that is, 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. In other words, it inhibits the “adipogenesis regulatory gene.”
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: the “Wnt paracrine pathway.”
The researchers hope that their mapping will improve understanding of the role that Cbf-beta plays in maintaining bone, especially as we age.
“The insights resulting from this study will fill an important knowledge gap and may facilitate the development of novel bone loss therapeutics that minimize the adverse side effects on bone homeostasis.”
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