25 September 2019

Not just Alzheimer's

A recent study found that people aged 75-85 years had 2 times more apoE protein in the blood than in 35-45 years, the same is true for 24-month-old mice compared with 4-month-old mice.

ApoE (apolipoprotein E) is one of the most important proteins involved in lipid metabolism, including cholesterol.

There are three main isoforms of the protein – apoE2, apoE3 and ApoE4. The ApoE4 isoform is the most important genetic risk factor for Alzheimer's disease.

Scientists wanted to find out what effect apoE has on the multi-stage process of bone healing.

In case of fracture, bone cells secrete signaling molecules into the bloodstream, attracting cells to the site of damage, contributing to the regeneration of bone tissue. Some of them, in particular skeletal stem cells, create cartilage as temporary scaffolding to hold parts of a broken bone. At the next stage, the collected cells mature into osteoblasts – cells that create bones that fit into dense bricks on top of cartilage.

ApoE.jpg

After that, another type of cells – osteoclasts, cells that resorb bones, destroys cartilaginous skeletons, and osteoblasts fill the vacated space with bone tissue. After several months of healing of a broken bone, there is almost no cartilage left in it. If the bone healing process works perfectly, after 5 years the signs of injury are no longer noticeable.

But scientists have found that if you add apoE to a Petri dish with skeletal stem cells, fewer cells develop into osteoblasts, and those cells that do develop are worse in quality. To test the hypothesis, an adenoviral vector with a small interfering RNA that prevents the production of apoE was injected into mice. Protein levels decreased by 75%, and the healed bones contained one and a half times more strong, hard bone tissue than the bones of mice that were not injected with anything.

These results confirmed that apoE inhibits the healing of bone fractures by altering the metabolism of osteoblasts, thereby identifying apoE as a new therapeutic target for improving bone repair in the elderly.

But for treatment, it is worth choosing a safer method of therapy, because too small an amount of apoE leads to the fact that fat is not processed properly in the body and accumulates in the blood vessels in the form of cholesterol plaques, which can cause cardiovascular diseases. In future studies, scientists would like to reduce the level of apoE in the blood temporarily, not irreversibly.

For example, to improve bone healing, a patient could take a pill or receive an injection to reduce apoE levels for a short time, rather than forever. This would probably be a much safer model.

The article by Huang et. al Lowering circulating apolipoprotein E levels improves aged bone fracture healing is published in the journal JCI Insight.

Elena Panasyuk, portal "Eternal youth" http://vechnayamolodost.ru based on Duke Health: Protein prevalent in older people could be key to healing bones.


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