"As people age, bones fracture easily even from minor impacts, and recovery is delayed. If weakened bone regeneration becomes possible using mitochondria, it is expected to help not only prevent fractures but also improve recovery speed."
Professor Lee Yun-sil of Seoul National University School of Dentistry, selected as the May recipient of the Korea Science & Technology Award hosted by the Ministry of Science and ICT and co-organized by the National Research Foundation of Korea and The Seoul Economic Daily, made these remarks regarding her research on mitochondria-driven bone formation. Lee's research team has demonstrated that mitochondria, long known as the "powerhouses of the cell," can function as a key signaling agent in bone formation. While existing osteoporosis treatments have focused on slowing bone loss, her work is seen as opening the possibility of shifting toward "active regenerative therapy" that rebuilds damaged bone.
Bone is not a rigidly fixed structure but a living tissue that continuously repeats formation and resorption. The cells that form new bone in this process are called osteoblasts. Mitochondria had been regarded only as organelles that supply energy within osteoblasts. However, Lee's research team confirmed that when osteoblasts are activated, mitochondria transform into a "donut shape" and are then secreted outside the cell as small mitochondrial fragments, helping surrounding osteoprogenitor cells differentiate into osteoblasts.
Lee's team developed the world's first mouse model in which mitochondria emit green light only in osteoblasts. This allowed them to observe in real time the location, movement, and morphological changes of mitochondria inside living cells. Previously, when cells were extracted from bone tissue, multiple cell types were mixed together, making it difficult to analyze osteoblasts alone with precision. This model improved the accuracy and reproducibility of the research.
"At first, I thought mitochondria acted only inside cells, but when I saw that mitochondrial components were detected in larger-than-expected quantities during bone tissue analysis, I hypothesized that they could be secreted outside the cell during bone formation," Lee explained. "The results were so striking at first that I even suspected experimental error, but through repeated verification using various methods, I became confident about the external secretion of mitochondria and their mechanism for promoting bone formation," she added.
The team also confirmed that when mitochondria secreted from osteoblasts were transplanted into damaged bone sites, the differentiation of osteoprogenitor cells was promoted and bone regeneration accelerated. This shows that mitochondria can act as a "key facilitator" that induces intercellular signaling and tissue regeneration, beyond merely being organelles that generate energy within cells.
This achievement carries significant meaning in an aging society. Patients with bone diseases such as osteoporosis, osteopenia, and fractures are increasing, but most current treatments are bone-resorption inhibitors that slow the rate at which bone is worn away. While this is an important treatment strategy, it has limitations in rebuilding bone that has already weakened, and long-term use may cause rare side effects, potentially requiring a "drug holiday" for a certain period.
By contrast, the mitochondria-based therapy proposed by Lee directly promotes bone formation. It focuses on using osteoblast-derived mitochondria to induce new bone regeneration at damaged sites. "The direction of osteoporosis treatment can shift from 'suppression' that prevents bones from worsening further to 'active regeneration' that restores damaged bone," Lee said. "It could also become a new option for patients whose recovery is slow after fractures or whose bones do not fuse well after surgery."
Lee has also secured domestic and international patents related to mitochondria-based therapeutic technology. She has registered a total of six patents in Korea and the United States and filed 11 applications. Last year, she was the only Korean researcher to participate in the working group drafting an international consensus report involving mitochondrial researchers worldwide, with the results published in Nature Metabolism.
A dentist by training, Lee says the questions she encountered in clinical practice led her to basic research. Her curiosity about why treatment responses and recovery speeds differ among patients expanded into research at the cellular and genetic levels. "Clinical practice and basic research are not separate paths but a connected process," she said. "I want to create a virtuous cycle in which research that begins with practical concerns returns in a way that helps patients."
Lee plans to further investigate the role of mitochondria not only in bone but also in various tissues, and to expand the academic horizons of mitochondria-based therapy. "Ultimately, I want to contribute to changing the way musculoskeletal diseases are treated," she said. "My goal is to usher in an era in which treatments that restore damaged tissue, beyond merely slowing disease progression, become commonplace."
