Pioneering new research has charted the unique genetic profile of the skeleton’s ‘master regulator’ cells, known as osteocytes.
The study led by the Garvan Institute of Medical Research was published in Nature Communications. The study describes the genes that are switched on or off in osteocytes, a multifunctional type of bone cell that regulates how bone material is grown or broken down in order to maintain healthy skeletons.
“This new information provides a kind of genetic shortlist we can look to when diagnosing bone diseases that have a genetic component,” said the study’s first author Dr Scott Youlten, Research Officer in the Bone Biology Lab. “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.”
Far from static, the skeleton is a highly dynamic structure that is constantly remodelled throughout a person’s life. Though osteocytes are the most common cell type in bone, they have been hard to study as they are embedded within the skeleton’s hard mineral structure.
Osteocytes form a network inside bones on a scale and complexity which mirrors the neurons in the brain (42 billion osteocytes with over 23 trillion connections between them), which monitors bone health and responds to ageing and damage by signalling other cells to either add more bone or break down old bone. Osteoporosis, rare genetic skeletal disorders and other bone diseases arise from an imbalance in these processes.
To understand what genes are involved in controlling bone build-up or breakdown, the researchers isolated bone samples from different skeletal sites of experimental models in order to measure the average gene activity in osteocytes. In so doing, they found an osteocyte ‘signature’ of 1239 genes that are switched on. Of these genes, 77% had no previously known role in the skeleton, and many were completely novel and unique to osteocytes.
“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,” explained Dr Youlten.
Comparing the osteocyte signature genes with human genetic association studies of osteoporosis could identify new genes that may be associated with susceptibility to this common skeleton disease. Additionally, a number of these osteocyte genes were also shown to be responsible for 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.
Co-senior author Professor Peter Croucher, Deputy Director of the Garvan Institute and Head of the Bone Biology Lab, said that “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. 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 development of bone disease and also restore lost bone.”
Source: Medical Xpress
Journal information: Nature Communications (2021). DOI: 10.1038/s41467-021-22517-1
