Researchers map unique genetic profile of osteocytes for the first time

Researchers from the Garvan Institute of Medical Research have mapped the specific genetic profile of the skeleton’s “master regulator” cells, called osteocytes, for the first time.

Researchers map unique genetic profile of osteocytes for the first time
Professor Peter Croucher and Dr. Scott Youlten. Image Credit: Garvan Institute of Medical Research.

The research, which was published in Nature Communications, details the genes that are turned off or on in osteocytes, a form of bone cell that regulates how other types of cells break down or make parts of the skeleton to keep bones healthy and strong.

This new information provides a kind of genetic shortlist we can look to when diagnosing bone diseases that have a genetic component. Identifying this unique genetic pattern will also help us find new therapies for bone disease and better understand the impacts of current therapies on the skeleton.”

Dr Scott Youlten, Study First Author and Research Officer, Bone Biology Lab

A first look at the osteocyte transcriptome

Being a highly dynamic structure, the skeleton changes in composition and shape over the course of a person’s life. Osteocytes are the most common cell type in bone, but they have been hard to analyze as they are hidden within the skeleton’s hard mineral structure.

Within the bone, osteocytes create a network similar in complexity and scale to the brain’s neurons (with over 23 trillion contacts between 42 billion osteocytes) that regulate bone health and respond to aging and injury by signaling other cells to develop new bone or break down old bone.

Inconsistency in these pathways causes diseases like osteoporosis and rare genetic skeletal disorders.

Many of the genes we saw enriched in osteocytes are also found in neurons, which is interesting given these cells share similar physical characteristics and may suggest they are more closely related than we previously thought.”

Dr Scott Youlten, Study First Author and Research Officer, Bone Biology Lab

A correlation of osteocyte signature genes with human genetic interaction studies of osteoporosis uncovers new genes that could be linked to susceptibility to this common skeleton disorder. Besides that, many of these osteocyte genes have been linked to rare bone diseases.

Mapping the osteocyte transcriptome could help clinicians and researchers more easily establish whether a rare bone disease has a genetic cause, by looking through the ‘shortlist’ of genes known to play an active role in controlling the skeleton,” said Dr. Youlten.

The big picture view

The osteocyte transcriptome map gives researchers a picture of the whole landscape of genes that are switched on in osteocytes for the first time, rather than just a small glimpse. The majority of genes that we’ve found to be active within osteocytes had no previously known role in bones.”

Peter Croucher, Study Co-Senior Author and Professor, Garvan Institute of Medical Research

Croucher is also the Garvan Institute’s Deputy Director and the head of the Bone Biology Lab.

This discovery will help us understand what controls the skeleton, which genes are important in rare and common skeletal diseases, and help us identify new treatments that can stop the development of bone disease and also restore lost bone,” concluded Croucher.

Source:
Journal reference:

Youlten, S. E., et al. (2021) Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease. Nature Communications. doi.org/10.1038/s41467-021-22517-1.

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