Bone Cell Map Reveals Blood Vessel Role in Skeletal Health

Garvan Institute of Medical Research researchers have mapped the cells and genes that control bone formation and loss, uncovering a previously underappreciated role for cells surrounding blood vessels in bone repair. The study, published in Nature Genetics, combined genomic sequencing with data from half a million people and identified hundreds of previously unknown genes involved in bone health. 

The findings could support new therapies to rebuild lost bone, potentially benefiting nearly half of all people over 50 living with skeletal conditions including osteoporosis, osteoarthritis, osteogenesis imperfecta, and cancers that spread to bone.

“Most people don't realize that bones are constantly changing—the human body replaces its skeleton every 10 years or so,” senior author Peter Croucher explained, adding that until now scientists have had a very limited understanding of the cells and mechanisms behind this turnover. He noted that most current drugs focus only on halting bone disease rather than rebuilding lost bone, “which is really important for reversing damage.”

Using single-cell RNA sequencing, the team examined gene activity within individual cells at the interface between hard bone and bone marrow, the key site of bone formation and breakdown, identifying 34 distinct cell groups and the genes active in each. “To our surprise, more than half of the genes identified have never before been shown to play a role in maintaining bone health, which is a significant finding,” first author Ryan Chai said.

The team then used the map to pinpoint cells involved in osteogenesis imperfecta and osteoporosis, analyzing genetic and bone density data from half a million UK Biobank participants. This, co-author John Kemp said, made it possible to identify exactly which cells drive skeletal disease: “These include cells known to regulate bone formation and bone loss, as well as blood vessel cells that, until now, have had underappreciated roles in bone health.”

Professor Croucher noted the findings also open opportunities related to cancer, since bone is a common hiding place for dormant cancer cells and a frequent site of relapse. The team is now investigating these cells and genes further and has made its data accessible to researchers worldwide through an open access platform. “We hope that sharing this knowledge can speed up development of new therapies that prevent diseases like osteoporosis and reverse the damage caused by them,” Kemp added.