Researchers led by NYU Langone Health report that the gene HOXA10 helps preserve skeletal stem cells throughout life, supporting the bone’s capacity to repair itself. The study, published in Science Advances, used genetically engineered mice and experiments on human bone cells to examine how the gene affects stem cell maintenance and bone healing.
Skeletal stem and progenitor cells contribute to bone maintenance and regeneration. The researchers found that HOXA10 helps these cells renew themselves and prevents them from maturing into bone-forming osteoblasts before they are needed. The team describes this as a way of protecting the stem cell supply from being depleted too early.
To study the gene’s effects over time, the researchers switched off HOXA10 in mice when they were six days old and tracked their bone stem cells for 15 months. By the end of that period, about 90% of the stem cells and descendants expected to be present had been lost, which the researchers attributed to reduced self-renewal.
The altered mice also had difficulty healing fractures. Stem cell progenitors made up 48% of the callus—the temporary tissue that forms across a break during healing—compared with 76% in control mice. Additional experiments showed that loss of HOXA10 disrupted the organization of collagen, which provides an early framework for new bone.
In tests using human bone biopsies, researchers silenced three related HOX genes. The cells showed larger reductions in stem cell numbers than the mouse cells, and programmed cell death increased by 50%. The findings suggest that human skeletal stem cells may rely on HOX genes for self-renewal and survival, although the experiments do not establish a treatment for patients.
The researchers say the results identify HOXA10 as a functional regulator of skeletal stem cell maintenance and point to HOX genes as possible targets for future approaches to bone regeneration. The study builds on earlier work led by senior author Philipp Leucht, which found that increasing HOXA10 activity could improve fracture healing in older mice.