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Approximately 10 million Americans have osteoporosis, also known as a silent disease due to symptoms that go unnoticed until a fracture occurs. Scientists are focused on understanding the mechanisms that contribute to the loss of bone strength, as well as developing therapies for prevention and treatment.

Illustration of adipocyte fat cells.

Weibo Hunag, Feng Hua and Tong Suand a team in China published an in the Journal of Lipid Research. They investigated the relationship between bone marrow adipocytes, or BMAds, and osteoblast bone building cells. BMAds are fat cells that reside in the bone marrow, and contribute to 10% of the total body fat and occupy 50–70% of the marrow cavity space. Their abundance has been associated with aging, postmenopausal period, obesity, radiotherapy and chemotherapy and glucocorticoid treatments.

The researchers treated bone marrow osteoblast cultures with adipocytes and observed that the adipocytes transferred lipid droplets to the osteoblasts. RNA sequencing and Western blot showed that the lipid droplet–filled osteoblasts downregulated osteopontin, a major bone-forming protein, and other osteogenic proteins. Furthermore, the lipids seemed to upregulate the ferroptosis pathway in the osteoblasts, inducing cell death, and it decreased oxidative phosphorylation, which generates cellular energy. When the researchers treated the osteoblasts with ferroptosis inhibitors, they found that impediments to the osteoblast cells were reversed. 

This work shows the ferroptosis pathway and proteins such as ABHD5 as important targets for the development of effective treatments and prevention therapies for osteoporosis. Looking ahead, the researchers will conduct further investigations into the activation mechanisms of these pathways to provide a solid foundation for clinical translation.