Bone mainly contains three types of cells: osteocytes, osteoblasts, and osteoclasts. The osteocytes are the most abundant cells comprising 95% of the total cell population in bone with an average half-life of 25 years. Osteocytes can also be responsible for not only bone diseases and disorders, but also those of the kidney, heart, and potentially muscle. Now researchers at the Garvan Institute of Medical Research have for the first time mapped the unique genetic profile of osteocytes. This new genetic map can help lead to new therapeutics and a better understanding of bone diseases and the impacts of current skeletal therapies.
The researchers published their findings in the journal Nature Communications, in a paper titled, “Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease.”
“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 Scott Youlten, PhD, research officer in the bone biology lab at Garvan. “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.”
Osteocytes form a network, similar to the neurons in the brain, that monitors bone health and responds to aging and damage by signaling other cells to build more bone or break down old bone.
“Osteocytes are master regulators of the skeleton,” wrote the researchers. “We mapped the transcriptome of osteocytes from different skeletal sites, across age and sexes in mice to reveal genes and molecular programs that control this complex cellular network.”
The researchers mapped a comprehensive osteocyte “signature” of 1,239 genes that are switched on in osteocytes and that distinguish them from other cells.
“Seventy-seven percent have no previously known role in the skeleton and are enriched for genes regulating neuronal network formation, suggesting this program is important in osteocyte communication. We evaluated 19 skeletal parameters in 733 knockout mouse lines and reveal 26 osteocyte transcriptome signature genes that control bone structure and function,” noted the researchers.
“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 Youlten.
This map provides major new insights into the genes and molecular pathways that regulate osteocyte differentiation, and the fundamental processes underlying skeletal physiology.
“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,” added Youlten.
Co-senior author Peter Croucher, PhD, deputy director of the Garvan Institute and head of the bone biology lab, said: “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.”