The recent investigation gives a better understanding of a cell mechanism in which the dysfunctional mitochondria due to smoking, drinking alcohol and other modifiable components raise the risk osteoporosis (a bone disease).
The mechanism spurs a type of cell in the immune system to osteoclasts. Osteoclasts are classified as a cell which dissolves and reabsorbs bones. It is believed that tiny organelles mitochondria present in the cytoplasm responsible for energy production send the signals under the condition of stress to initiate this cell mechanism.
At the point when this occurs in the mitochondria of macrophages, the cells transform into osteoclasts. Macrophages are productive immune cells that expel cell waste and foreign particles by engulfing and digesting them.
The research group was from the University of Pennsylvania (Penn) in Philadelphia and the Icahn School of Medicine at Mount Sinai in the city of New York. The research paper “Cytochrome c oxidase dysfunction enhances phagocytic function and osteoclast formation in macrophages” was published in the FASEB journal on 7th May 2019.
“We show in this paper that when mitochondrial function is affected, it not only affects energy production but also triggers a type of stress signaling that induces the overproduction of osteoclasts,” says lead study author Narayan G. Avadhani, who is a lecturer of biochemistry at Penn’s School of Veterinary Medicine.
Some common factors like smoking, drinking liquor and certain medications make the mitochondria dysfunctional which further raise the risk of osteoporosis.
Prof. Avadhani and his associates say that the stress signaling pathway that they revealed could be one of the reasons. The proved and tested their findings in laboratory cultured macrophages and mice having impaired mitochondria.
Osteoporosis is a malady which makes the bones porous, thin, less dense and brittle. This increases the chances of fracture as bones become easily breakable.
The risk for osteoporosis increases with age. This is on the grounds that the balance between bone generation and bone resorption gets disturbed. Usually, the bone density reaches its peak by the age of 30. After this, the balance gets disturbed and the bone density starts to decline as the process of bone resorption becomes greater than bone-generation.
As per the data of International Osteoporosis Foundation (IOF), 1 of every 3 women and 1 out of 5 men aging above 50 years old encounters a fracture (breakage of bone) because of osteoporosis.
The International Osteoporosis Foundation further explains that around 75 million individuals in the United States, Europe, and Japan have osteoporosis and that osteoporosis prompts more than 8.9 million bone fractures every year around the world.
Researchers in their study paper explains that mitochondria-to-nucleus retrograde signaling (MtRS) pathway make easy for cells to adjust themselves in stress-related conditions.
A prior examination has helped them to find that a way for setting off this pathway can incite macrophages to change into osteoclasts that resorb bone.
“However,” they note, “mechanisms through which macrophages sense and respond to cellular stress remain unclear.”
Dysfunctional mitochondria advance to the formation of osteoclasts
To investigate how mitochondrial damage may be included, they ran a few examinations on laboratory-cultured mouse macrophages. They began their research in the macrophages by causing impairment in them with the help of the destruction of an enzyme called cytochrome oxidase C. This enzyme is responsible for managing mitochondrial energy generation.
As soon this occurs, the macrophages start releasing different signaling molecules which do not only initiates inflammation but also promotes the formation of osteoclasts from the different type of cells.
Further research revealed that something surprising was going on with a molecule called RANK-L. Bone-generation and bone resorption go together with that it bone-generation release RANK-L molecules which triggers bone resorption. This is how the two processes are balanced.
However, the researchers found that impaired mitochondria sent signals, due to which macrophages kept on changing into osteoclasts and, thus promotes bone resorption even when there are not many RANK-L molecules around.
The last set of tests mitochondrial dysfunction mouse models further affirmed their findings. Now the researchers are eager to work on preserving the mitochondrial function to know that if this would help in reducing the risk of osteoporosis.
“In some respects, mitochondrial stress signaling may even be replacing RANK-L. That we don’t know now, but we plan to look into that further, said Prof. Narayan G. Avadhani.