With world-class breakthrough results published in natural geneticsResearchers have successfully mapped the cells and genes that control bone formation and loss on an unprecedented scale and discovered the important role that vascular cells play in bone health.
By combining genome sequencing and data from 500,000 people, the research team identified hundreds of previously unknown genes that control bone health and revealed that perivascular cells are one of the driving forces of bone repair. This role has traditionally been underestimated.
The team’s findings, led by Professor Peter Croucher and Dr Ryan Chai from the Garvan Institute of Medical Research, Associate Professor John Kemp from Mater Research, and Professor Graham Williams and Professor Duncan Bassett from Imperial College London, fundamentally improve our understanding of skeletal diseases.
The discovery enables the development of new treatments to rebuild lost bone and is expected to bring hope to nearly half of people over the age of 50 living with rare and common skeletal conditions such as osteoporosis, osteoarthritis and osteogenesis imperfecta, as well as people with rare bone diseases and cancer that has spread to the bones.
“Most people don’t realize that bones are constantly changing. The human body replaces its skeleton about every 10 years,” Professor Croucher says.
Although this is a critically important process, until now there has been a very limited understanding of the cells and mechanisms that control this bone turnover. Most drugs currently available focus only on stopping bone disease rather than rebuilding lost bone, which is critical to repairing damage. ”
Peter Croucher, Professor, Garvan Institute
The most detailed map of cells and genes that regulate bone health
Using state-of-the-art single-cell RNA sequencing, the researchers focused on the interface between hard bone and bone marrow, a key site of bone formation and destruction, and measured which genes were turned on within individual cells found in bone.
Dr. Chai said the team’s extensive analysis found 34 distinct cell groups and identified genes active in each of these cell types.
“Surprisingly, more than half of the genes identified have never been previously shown to play a role in maintaining bone health, which is an important finding,” added Dr. Chai.
A surprising new role for vascular cells
The researchers used the map to identify cells involved in rare and common skeletal diseases such as osteogenesis imperfecta and osteoporosis. For the latter, the team analyzed the UK Biobank, one of the world’s largest and most comprehensive collections of biological samples.
Associate Professor Kemp said that by analyzing genetic and bone density data from 500,000 people participating in the UK Biobank, the team was able to pinpoint which cells were causing the skeletal disease.
“These include cells known to regulate bone formation and bone loss, as well as vascular cells whose role in bone health has been previously underestimated,” added Associate Professor Kemp.
Resources to accelerate the development of new treatments
Professor Croucher said the research revealed new treatment opportunities for bone diseases as well as cancer.
“Identifying the cells and genes that promote bone turnover also opens new opportunities to prevent cancer metastasis, as bone is a major harborage for dormant cancer cells and a common site for recurrence,” he said.
The research team is currently further studying the role of the newly discovered bone regulatory cells and genes with the aim of developing new drugs against these targets. Its groundbreaking data is now accessible to medical researchers around the world through an open access platform.
Associate Professor Kemp said: “We hope that by sharing this knowledge we can accelerate the development of new treatments to prevent diseases such as osteoporosis and reverse the damage caused by osteoporosis.”
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Reference magazines:
Chai, R.C. others. (2026) Multiscale analysis and functional validation of cellular and genetic determinants of skeletal diseases. natural genetics. DOI: 10.1038/s41588-026-02640-9. https://www.nature.com/articles/s41588-026-02640-9.
