Blood Vessel Cells Play a Crucial Role in Bone Development

Researchers have discovered a protein that inhibits the activity of bone-forming cells (osteoblasts) by preventing their maturation during the process of migrating to bone-formation sites.

Scientists led by Dr. Amy Naylor and Professor Roy Bicknell, along with Dr. Georgiana Neag from the University of Birmingham, have found that protein CLEC14A on endothelial cells in bone blocks the function of osteoblasts.

Endothelial cells transport immature osteoblasts to new bone sites. However, when CLEC14A is present on the endothelial cell surface, osteoblasts are prevented from maturing to form bone tissue.

In this study, osteoblast cells were isolated from transgenic mice bred to either express CLEC14A or not. The osteoblasts were cultured in vitro in an induction solution. Cells from mice lacking CLEC14A reached maturity in four days, whereas cells from mice expressing CLEC14A matured in 12 days. Additionally, the CLEC14A-free samples exhibited a substantial increase in mineralized bone tissue by day 18.

In the last decade, a specific type of blood vessel cell was identified within bones. This blood vessel is called ‘type-H’ and is responsible for guiding bone-forming osteoblasts to the places where bone growth is needed. Now we have discovered that a protein called CLEC14A can be found on the surface of type-H blood vessel cells.”

Dr. Amy Naylor, Associate Professor, School of Infection, Inflammation and Immunology, University of Birmingham

Dr. Amy Naylor said, “In the experiments we performed, when CLEC14A protein is present the osteoblasts that were sharing a ride on the endothelial cells produce less bone. Conversely, when the protein is removed, they produce more bone.”

Dr. Amy Naylor added, “This additional understanding of how blood vessel cells control bone-forming osteoblasts under normal, healthy conditions provides an avenue to develop treatments for patients who have insufficient bone formation, for example in patients with fractures that do not heal, osteoporosis or with chronic inflammatory diseases.”

We know that poor bone formation is an important driver of bone damage in osteoporosis and autoimmune inflammatory arthritis. This can lead to disability, pain, and fatigue which impacts people’s lives in many ways, including their ability to work, the time they spend with family and friends, and their wellbeing.”

Lucy Donaldson, Director, Research & Health Intelligence, Versus Arthritis

We are proud to have funded Dr. Naylor's research which has improved our understanding of bone formation and remodelling. We hope these findings will eventually lead to new treatment approaches for people with musculoskeletal conditions. Whilst these findings are promising, we would not rest until everyone with arthritis has access to treatments and interventions that let them live the lives they choose,” concludes Lucy Donaldson.

Source:
Journal reference:

Neag, G., et al. (2024) Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning. Communications Biology. doi.org/10.1038/s42003-024-06971-3.

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