Researchers discovered that in mice lacking a protein that is responsible for muscle contraction, fusion developed between the vertebrae of the spine, which may lead to scoliosis and other orthopedic diseases
The skeletal muscles move the body, allow it to stabilize, protect the skeleton and internal organs and help absorb shocks resulting from body movements. Within them is the sense of spatial perception (sixth sense / proprioception), which contains sensors or receptors that sense the degree of muscle contraction and its speed and communicate with other muscles and the brain. This creates a complex nervous activity that results in a delicate and controlled balance between many muscles in the body; The brain receives information from all these sensors regularly and thus calculates the level of muscle tension, knows where each body part is and helps maintain balance at any given moment.
What is the question? How can a disorder in muscle protein damage the bone structure?
"The sense of spatial perception is less well known than the other senses and in recent years the information about it is accumulating. Today we know that it is the one that allows us to move with full coordination between all muscle groups and to know where the body is in space," explains Dr. Ronan Belcher, an expert in orthopedic surgery, a spine surgeon at Asuta Ashdod Hospital and a researcher of the musculoskeletal system and diseases of the spine (especially scoliosis ) at the Weizmann Institute of Science. As part of his doctorate at the Weizmann Institute, Dr. Belcher examined mice whose sense of spatial perception was damaged and discovered that they had a scoliosis similar to the human one. In other words, he discovered that the muscular system is primarily responsible for the development of scoliosis - a disease in which the vertebrae deviate to the side from the midline and create a distortion in the structure of the spine that causes it to tilt.
Today, as part of his activity in Prof. Eli Seltzer's laboratory in the Department of Molecular Genetics at the Weizmann Institute, Dr. Belcher continues to investigate how musculoskeletal diseases arise, the main one of which is scoliosis. In one of their latest studies, which won a grant from the National Science Foundation, Dr. Belcher and his team lined up the sensors of the spatial sense to understand how they work. This is how they discovered several factors that criticize their activity, including 1 TNNT - one of the muscle proteins responsible for its contraction, known to be involved in musculoskeletal diseases including scoliosis. "This protein apparently plays a role in the control of the sensors and when we damaged it in mice - they developed orthopedic diseases such as scoliosis", explains Dr. Belcher.
The aim of the researchers' latest study was to check how the lack of protein affects the skeletal system and the development of orthopedic diseases such as scoliosis, by what mechanism. According to Dr. Belcher, "We wanted to check how a disruption in this muscle protein might change the structure of the bones. A skeleton that contorts due to a muscular disorder - that's the innovation."
To this end, the researchers examined adult mice (three months old) in which the TNNT 1 protein had been removed through genetic engineering, and found that their spinal vertebrae joined instead of being separated by the disc (the cartilage tissue that is between every two vertebrae). "We scanned the spinal column of the mice with CT and the main finding was fusion between the vertebrae. In addition they had mild scoliosis. Therefore, we wanted to know when the fusion appears, at what age, is it an early or late developmental defect, which vertebrae does it include, and what is the molecular mechanism behind it? This is a significant structural change that can lead to scoliosis and other orthopedic diseases, the origin of which is not fully known, such as ankylosing spondylitis. These are common diseases that cause significant morbidity in the population - such as deformation of the spine, pain and restriction of movement," explains Dr. Belcher.
The researchers then performed a CT scan on additional mice that lacked the protein - from birth to three months old - and the tissues where the fusion appeared were cut into slices and stained to allow them to be viewed under a light microscope (histological sections). This is to understand the sequence of events that leads to fusion and to discover the anatomical variables (such as discs and vertebrae) that are involved in it.
It turns out that the fusion in the spine appears at a young age and beyond, that is, it is not congenital but acquired. In other words, for the spine to develop properly in early and adult life, a functioning muscular system is required. The structure of the spine depends on the function of the muscles around it and their sensors.
So far, the researchers have discovered that the fusion appears at a young age and beyond, meaning that it is not born but acquired. "We discovered that in order for the spine to develop properly in early and adult life, a functioning muscle system is required. The structure of the spine depends on the function of the muscles around it and their sensors. In other words, we are beginning to understand that it is possible that the origin of the fusion is actually in the muscle system and not in the vertebrae, that muscle dysfunction affects the shape of the skeleton, in this case the spine. What is certain is that there is a connection between the two systems, muscle and skeleton," explains Dr. Belcher.
Today, the researchers continue to perform spinal CT scans on mice every 48-24 hours and will soon begin to investigate what is the exact time window in which the fusion appears and what is the molecular mechanism that leads to it. According to Dr. Belcher, "If we know that the absence of TNNT 1 leads to fusion on a certain day, on that day we will perform a histological analysis of the samples. This is how we hope to find out what is the molecular mechanism by which the muscle system has such a significant effect on the skeletal system. It is scientifically and clinically interesting: once we establish the connection between the absence of the muscle protein and the appearance of fusion between the vertebrae - we can test it in patients; As mentioned, fusion is a common orthopedic disorder, and the attempt to understand how it is formed due to a protein problem, and the molecular mechanism behind it, can help treat it and even early diagnosis and prevention (for example, in those with a family background of protein deficiency), similar to other diseases."
Life itself:
Dr. Ronan Belcher, married + three, lives in Kfar Aviv. In his free time he likes to swim, listen to music and travel with his family.
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