Risk factors for osteoporosis cannot be avoided. Some of them include being older or having a family history of the condition. Others, like consuming alcohol, smoking cigarettes, exposure to environmental pollutants, and taking certain medications, can be avoided. Until now, researchers have not identified how these exposures are linked with bone loss.
Researchers from Penn’s School of Veterinary Medicine revealed a mechanism through which osteoporosis and these factors are linked. Damage to the mitochondria results in a surge in the creation of cells known as osteoclasts. They are responsible for the breaking down of bones. The researchers identified these effects in cells in culture and in an animal model.
According to Narayan Avadhani, a biochemist and senior author on the work, the process of bone degradation and rebuilding in normal individuals proceeds in a balanced way. Some people, however, produce way more osteoclasts. This then leads to osteoporosis and bone loss. He said that once mitochondrial functions are affected, it affects not only energy production but also triggers stress signaling which induces overproduction of osteoclasts.
Avadhani’s lab examined the effects of mitochondrial dysfunction on various phenomena including liver disease and cancer. The researchers took a close look at how the problems with mitochondria had effects on a type of immune cell called macrophages.
Macrophages are normally the immune system’s front line. They engulf and digest foreign invaders in the body. They can also diversify and transform into osteoclasts during the right circumstances.
The researchers damaged a key enzyme, cytochrome oxidase C, in charge of energy production in mitochondria in lab-grown mouse macrophages. This led to the macrophages releasing various signaling molecules that are associated with inflammatory reactions. It also encouraged them to go follow the path to becoming osteoclasts.
When the researchers took a close look at what was going on, they saw an anomaly with a key molecule, RANK-L. These molecules help in regulating the bone–rebuilding process. Bone-building cells release it as a means to induce bone breakdown. Damaged mitochondria went through stress signaling transforming into osteoclasts at faster rates even with low levels of RANK-L. The osteoclasts resulted in greater rates of bone breakdown.
Avadhani said that they planned to look into RANK-L getting replaced by mitochondrial stress signaling.
The team confirmed their findings in a mouse model. It showed that animals that had a mutation that leads to dysfunctional mitochondria had increased osteoclasts production. Their macrophages also had high levels of phagocytosis. This is the process by which immune cells engulf and eat invaders.
Some of the same environmental risk factors that promote osteoporosis can have an impact on mitochondrial function. The researchers argue that stress signaling could be the pathway through which they act to affect bone health.
Future research from the team may look into how safeguarding mitochondria function might protect against osteoporosis.
Feel free to share your thoughts in the comment section below.