NEW YORK, Nov. 4, 2026 /PRNewswire/ -- The action of a key gene is required to maintain a lifelong supply of stem cells that make bone healing possible, a new study finds.

These immature cells are known to get the signal to either continually divide to make more copies of themselves (self-renewal) as a ready pool of replacements, or to mature into cells with a specific function like bone-building. Once they mature, they generally cannot reverse the process, so the supply of stem cells is limited. Such pools become even more depleted as people age.

Led by NYU Langone Health researchers, the new work identified the gene HOXA10 as a lifelong protector of the stem cell supplies, keeping them from maturing into bone-building cells called osteoblasts until needed for healing. 

For the study, publishing online November 4 in Science Advances, the authors examined the state of bone stem cells in mice for 15 months after they deleted HOXA10 in 6-day-old pups. By the end of that period, 90 percent of the stem cells and descendants that should have been present were gone due to a loss of self-renewal.

"Most bone research asks how stem cells become bone," said corresponding study author Philipp Leucht, MD, PhD, the Jyoti Menon Associate Professor of Orthopedic Surgery in the Department of Orthopedic Surgery at NYU Grossman School of Medicine. "We asked how they remain as stem cell replacements in the first place. Without the study gene, bone burns through its reserves too early, which is what we see in aging bone."

"Our study shows that HOXA10 protects healing capacity normally by acting as a brake on premature maturation," said Dr. Leucht, who is also the vice chair for research in the Department of Orthopedic Surgery. "To our knowledge, this study is the first to assign a definitive role for HOX genes in the active maintenance of adult skeletal stem cells."

In addition, researchers found that mice engineered to lack HOXA10 action could not heal properly after breaking a bone. The proportion of stem cell progenitors in the callus—the temporary tissue bridge spanning a break as it begins to heal—was only 48 percent for the engineered mice, compared with 76 percent for control mice with the functional gene.

Other experiments confirmed that deleting HOXA10 causes collagen proteins that lay the early framework for rebuilding bone to become disorderly. This is a problem because the rope-like scaffold at a break site must be arranged in neat lines, rather than as a tangled mesh, for new bone to harden with calcium.

The researchers also obtained bone biopsies from human patients and silenced three related HOX genes at once. The human cells responded like mouse cells, only with more dramatic reductions in stem cell numbers. The human cells also began to die, with apoptosis (programmed self-destruction) up by 50 percent. This suggests that human stem cells may depend even more on HOX genes for long-term self-renewal, Dr. Leucht said.

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For the current study, the research team genetically engineered mice to have their HOXA10-expressing stem cells tagged with a fluorescent green marker, as well as to have built-in mechanisms that the team could use to switch the genes off on command. This let them accurately track the status of the cells at all stages of life in the study mice.

In this way the team learned that HOXA10-positive cells outperform other stem cells in the periosteum, the membrane that covers the surface of most bones, at colony-forming. This test, in which a single cell is prompted to generate a colony of cells by dividing and multiplying continually, is considered a standard readout of self-renewal capacity.

HOX genes have been shown by past studies to control periosteal stem and progenitor cells, or PSPCs, which play a key role in bone healing. HOX genes are known to encode proteins that act like the body's "zip code," specifying the position of limbs in the womb. The new study builds on another led by Dr. Leucht and published in 2023, which showed that increasing the activity of the HOXA10 gene could improve fracture healing in older mice.

"Our study identifies HOXA10 as a preserver of skeletal stem cell pools over time by promoting self-renewal, suppressing premature maturation, and lining up the protein fibers in a break so that the two ends of broken bone can knit," said Dr. Leucht. "The findings establish HOX genes as potential therapeutic targets for enhancing bone regeneration."

Along with Dr. Leucht, study authors from the Department of Orthopedic Surgery at NYU Langone School of Medicine were first author Kevin Leclerc, PhD; Margaux Sambon, PhD; Raven Weng; Vincentius Jeremy Suhardi, MD, PhD; Malissa Ramsukh; Rohan Padke; Gabrielle Pack; Jack Zhong, MD; Benjamin Schaffler, MD; Sergio Butron; and co-corresponding author Sophie Morgani, PhD. Also an author was Matthew Rytel in the Department of Cell Biology. 

This work was partially supported National Institutes of Health grants R21AR081268 (National Institute of Arthritis and Musculoskeletal and Skin), R01AG086058 (National Institute for Aging), and by a career development award from the Musculoskeletal Transplant Foundation. Dr. Leucht is supported by a gift from the P. and F. Zarb Family.

About NYU Langone Health 
NYU Langone Health is a fully integrated health system that consistently achieves the best patient outcomes through a rigorous focus on quality that has resulted in some of the lowest mortality rates in the nation. Vizient Inc. has ranked NYU Langone No. 1 out of 122 comprehensive academic medical centers across the nation five years in a row, and it continues to have the most No. 1– and top 10–ranked specialties among medical centers in the United States, according to U.S. News & World Report. NYU Langone offers a comprehensive range of medical services with one high standard of care across seven inpatient locations, its Perlmutter Cancer Center, and more than 400 outpatient locations in the New York City area and Florida. The system also includes two tuition-free medical schools, in Manhattan and on Long Island, and a vast research enterprise.

Media Contact:
Gregory.williams@nyulangone.org

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SOURCE NYU Grossman School of Medicine and NYU Langone Health