Research reveals how osteocytes form critical structures that maintain bone health

BOSTON – Embedded within bone tissue are osteocytes, cells with tree-like projections called dendrites that are important for receiving communication from other cells. The loss of dendrites that occurs during aging contributes to bone fragility and osteoporosis. In a study published in Nature Communications, an international team led by investigators at Massachusetts General Hospital (MGH) has revealed how osteocytes form dendrites—a discovery that might lead to strategies to maintain these projections and therefore help protect individuals’ bone health throughout life.

In their study, the researchers found that deletion of Sp7, a gene linked to both rare and common skeletal diseases, in osteocytes causes severe defects in osteocyte dendrites.
This gene codes for a protein called a transcription factor, which controls the expression of other genes. The team found that the Sp7 transcription factor targets a gene called osteocrin, which promotes osteocyte dendrite formation. In mice, turning the osteocrin gene on made up for the absence of Sp7 and reversed defects in osteocyte dendrites.

“In this work, we demonstrate key roles for the transcription factor Sp7 and its target osteocrin in orchestrating a gene regulatory network needed to promote healthy connections between bone cells,” says senior author Marc Wein, MD, PhD, an investigator in the endocrine unit at MGH and an assistant professor of medicine at Harvard Medical School. “Understanding how osteocytes maintain this network of connections opens up exciting possibilities for new ways to treat osteoporosis and other diseases where bones are prone to fracture.”

Co-authors include Jialiang S. Wang, Tushar Kamath, Courtney M. Mazur, Fatemeh Mirzamohammadi, Daniel Rotter, Hironori Hojo, Christian D. Castro, Nicha Tokavanich, Rushi Patel, Nicolas Govea, Tetsuya Enishi, Yunshu Wu, Janaina da Silva Martins, Michael Bruce, Daniel J. Brooks, Mary L. Bouxsein, Danielle Tokarz, Charles P. Lin, Abdul Abdul, Evan Z. Macosko, Melissa Fiscaletti, Craig F. Munns, Pearl Ryder, Maria Kost-Alimova, Patrick Byrne, Beth Cimini, Makoto Fujiwara, and Henry M. Kronenberg.

This work has been supported by the MGH Department of Medicine Transformative Scholar award, the American Society of Bone and Mineral Metabolism, generous support from Louise Pearl Corman PhD, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

This work was supported by the MGH Department of Medicine Transformative Scholar award, the American Society of Bone and Mineral Metabolism, Louise Pearl Corman PhD, and the National Institute of Arthritis and Musculoskeletal and Skin Disease.

About the Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2021, Mass General was named #5 in the U.S. News & World Report list of "America’s Best Hospitals."