Cell: New bone cell: osteomorph could be the target for osteoporosis?

Cell: New bone cell: osteomorph could be the target for osteoporosis?   Cell: Discovery of a new type of bone cell—osteomorph, which provides a new therapeutic target for the treatment of bone diseases such as osteoporosis.

In a new study, researchers from Gavin Medical Research in Australia and Imperial College London and other research institutions have discovered a new type of bone cell. This discovery may reveal the treatment of osteoporosis and other bone diseases. New method. The relevant research results were published online in Cell on February 25, 2021, with the title of the paper “Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption”.

Picture from Cell, 2021, doi: 10.1016/j.cell.2021.02.002.

These new cells called “osteomorph” exist in the blood and bone marrow and fuse together to form osteoclasts, which are cells that specialize in breaking down bone tissue. They have unique genomic characteristics, thus revealing a promising, yet unexplored therapeutic target.

Professor Tri Phan, the co-corresponding author of the paper and the head of the Gavin Institute of Medical Research’s Intravital Microscopy and Gene Expression Laboratory, said, “This discovery has changed the rules of the game. It not only helps us understand bone biology, but also contributes to osteoporosis. The treatment provides an important new approach. Osteomorph expresses several genes that seem to be related to bone diseases, which may allow scientists to find new ways to target osteoporosis.”

Bone resorption under the microscope

At the micro level, our bones are constantly changing. In order to support the growth, maintenance, and repair of bones, specialized cells on the surface of bones break down old bone tissue (called bone resorption) and rebuild new bone tissue. This change in balance can lead to weak bones, including osteoporosis. It is estimated that more than 900,000 people suffer from osteoporosis in Australia alone.

To better understand bone resorption, these authors studied osteoclasts, which are cells that specialize in bone resorption, in experimental models. Using in-vivo imaging technology that can deeply observe the inside of living bone tissue, they noticed that osteoclasts did something unusual — they split into smaller cells, and then reconnected to form osteoclasts.

Dr. Michelle McDonald, the first author of the paper and the head of the bone microenvironment group of the Gavin Institute of Medical Research, said, “This process is completely new to us. So far, everyone’s consensus is that osteoclasts will experience The cells die, but we see that they are circulated by dividing and connecting together again. We speculate that this process may increase their lifespan. We also found these cells in the blood and bone marrow, which indicates that they can travel to the bones. Other parts, as a possible cell’reserve’, when osteoclasts are needed again, these cells can fuse and deploy at any time.”

Unique genetic characteristics

These authors used cutting-edge single-cell RNA sequencing technology developed specifically to study these cells in the bones and found that these new cells have turned on some genes.

The co-author of the paper, Dr. Weng Hua Khoo, said, “The spectrum of genes that are turned on in these cells is really interesting—although many genes are also expressed by osteoclasts, several genes are unique. This, plus the living body The evidence of the new refusion process observed by imaging convinced us that we discovered a new cell type, which we named after Mighty Morphin Power Rangers (Dinosaur Team) and called it osteomorph.”

These authors eliminated 40 genes that were turned on in osteomorphs from the experimental model. They found that for 17 of these genes, this deletion affects bone mass and bone strength, indicating that these 17 genes play a key role in controlling bones.

Professor Peter Croucher, the co-corresponding author of the paper and the deputy director of the Gavin Institute of Medical Research, said, “When we further investigated the human genome data in the public database, we found that the genes turned on in the osteomorph are related to causing skeletal dysplasia and controlling bone mineral density. These findings together reveal how critical osteomorphs are in bone maintenance. Understanding these cells and the genes that control them may reveal new therapeutic targets for bone diseases.”

Explain a common side effect

In addition to revealing new treatment avenues, the authors’ findings also provide a possible explanation for a common clinical phenomenon. Professor Phan explained, “Some people who have stopped using the osteoporosis treatment drug denosumab will experience bone loss and an increase in the so-called ‘rebound vertebral fracture’.”

The authors say that denosumab blocks a molecule that they found that osteoblasts need to form osteoclasts. They speculate that patients receiving denosumab will accumulate osteomorphs in their bodies, and when treatment is stopped, these osteomorphs will be released to form osteoclasts that absorb bone.

The authors said that studying the effects of denosumab and other osteoporosis drugs on osteomorph may provide information on how to improve these drugs and how to prevent their withdrawal effects.

Croucher said, “Although we have not fully understood the role of osteomorphs, their existence has caused a major change in our understanding of bones. This research is a huge international joint effort across multiple scientific disciplines. We look forward to it. Explore how these cells can change future treatments for osteoporosis and other bone diseases.”

(source:internet, reference only)

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