SNU Engineering–medical research team identifies, for the first time, a new mechanism to enhance osteoporosis treatment efficiency

Seoul National University College of Engineering (SNU Engineering) announced that a joint research team led by Prof. Sunghoon Kwon (Department of Electrical and Computer Engineering, SNU) and Prof. Sang Wan Kim (Department of Endocrinology and Metabolism, Seoul National University College of Medicine and Boramae Medical Center) has discovered a new mechanism and drug combination strategy that can effectively treat osteoporosis, a representative disease of super-aging societies.

The research findings were published on April 2nd in Bone Research, a world-leading journal in the field of bone metabolism.

Osteoporosis is a disease in which bone mass decreases and bone microstructure deteriorates, making patients susceptible to fractures from minimal impact, such as coughing. It has become highly prevalent, affecting approximately one in three women over the age of 50, while it remians life-threatening, with mortality rates approaching 20% within one year following hip or spinal fractures. Therefore, proactive pharmacological treatment aimed at increasing bone mass is essential for osteoporosis treatment and fracture prevention.

However, drugs used in clinical practice present various limitations and side effects, making treatment challenging. The most commonly used “antiresorptive agents” suppress bone loss but have limited efficacy in increasing new bone mass, and discontinuation of these drugs can lead to rapid bone loss, known as “rebound bone loss.”

In addition, the currently most potent “anabolic agents” are strictly limited to a treatment duration of one to two years due to increased cardiovascular risk with long-term use. As treatment options remain limited, both clinicians and patients face significant challenges, making the development of safer and more effective therapeutic strategies urgently needed.

To establish a fundamental treatment strategy for osteoporosis, it is critically important to accurately understand the activation mechanisms of osteoblasts*. However, osteoblasts are tightly adhered in a very thin layer on the hard bone surface, making it nearly impossible to isolate and analyze them without damage using conventional cell separation techniques. This technical limitation has long been a major obstacle to elucidating osteoblast activation mechanisms and developing new therapeutic strategies.

* Osteoblast: A key cell responsible for bone formation and regeneration. It forms new bone tissue on the bone surface and mineralizes it, making it the most important target in osteoporosis treatment.

To address this challenge, Prof. Kwon’s research team utilized an in-house laser-based cell isolation system (Spatially resolved laser activated cell sorter, SLACS).

To precisely isolate specific cells while preserving their spatial information within tissues, the team combined microfabrication technology with laser optics. As a result, they designed a special “sacrificial layer”* that rapidly ablates in response to infrared laser irradiation. This enabled them to establish a novel technology capable of isolating cells with high precision, much like “punching out” a specific region from paper.

* Sacrificial layer: A layer coated on a glass slide supporting the tissue, which absorbs infrared laser energy and explodes. Positioned between the tissue and the slide, it generates force upon explosion that separates the target tissue.

This system, the only one in the world capable of isolating cells based on spatial information, minimizes physical damage to cells while enabling rapid extraction of extremely rare cell populations. Using this innovative engineering technology, the research team successfully isolated osteoblasts embedded within hard bone tissue and, for the first time, precisely decoded the key mechanisms regulating bone formation at the transcriptomic* level.

* Transcriptome: The complete set of RNA transcripts produced by activated genes within a cell, providing essential information for analyzing cellular functions and expression changes.

The analysis further revealed an additional mechanism regulating bone formation beyond previously known pathways.

The currently most effective osteoporosis drug used in clinical practice, romosozumab (brand name Evenity), works by inhibiting sclerostin, a protein that suppresses bone formation, thereby activating the WNT signaling pathway, which is essential for osteoblast activation.

However, through transcriptomic analysis across different stages of osteoblast activation, the research team discovered that, in addition to WNT signaling, the TGF-β signaling pathway also plays a critical role in osteoblast activation and bone formation efficiency. While romosozumab regulates one pathway (WNT signaling), this study identified another major pathway (TGF-β) contributing to bone formation.

Furthermore, the team proposed a combination therapy strategy targeting both pathways simultaneously. By administering a combination of romosozumab and a anti-TGF-β antibody (1D11 antibody), they demonstrated that bone mass increased more rapidly and effectively than with romosozumab alone through animal experiments, opening new possibilities for next-generation combination therapies for osteoporosis.

This achievement represents the result of a truly interdisciplinary collaboration combining engineering innovation and clinical insight. The medical research team identified clinical unmet needs encountered in real-world patient care and proposed hypotheses to overcome treatment limitations. The engineering team then utilized the SLACS system to uncover osteoblast activation mechanisms that had previously remained elusive.

By integrating the medical team’s extensive expertise in preclinical* experiments, the researchers successfully designed optimal drug combinations and validated their efficacy, presenting a case of translational research that bridges fundamental science and clinical application.

* Preclinical: Research conducted prior to clinical trials in humans, typically involving cell- or animal-based studies.

The SLACS system—the core technology of this study—has already moved beyond academic research and into real-world industrial application. The technology has been commercialized as a device called “CosmoSort,” developed by the biotechnology startup Meteor Biotech, and has established itself as a leading platform for highly precise biological sample analysis.

Its adoption by leading global research groups, including major pharmaceutical companies, further demonstrates its technological impact. The SLACS system is therefore expected to serve as a game-changing platform that can significantly shorten the drug development process not only for osteoporosis but also for cancer, immune disorders, and other intractable diseases.

First author Dr. Ahyoun Choi stated, “Through this study, we realized the importance of developing technologies capable of fully reconstructing the complex regulatory networks that occur in vivo during drug treatment. Building on this work, we plan to advance beyond simple drug combinations and develop next-generation bispecific antibody therapeutics capable of simultaneously targeting multiple pathways, enabling safer and more convenient treatment for patients.”

She added that she is preparing for overseas study to further expand her academic perspective and become a globally competitive bio researcher.

Prof. Sunghoon Kwon emphasized, “This study is only the beginning. Identifying drug mechanisms using the SLACS system will become a new standard strategy for discovering optimal drug combinations not only for osteoporosis but also for a wide range of diseases.”

This research was supported by the Ministry of Science and ICT’s Basic Science Research Program (Mid-Career Researcher Program), the Ministry of Health and Welfare (the Korea-US Collaborative Research Fund), the Ministry of Trade, Industry and Resources ( Industrial Strategic Technology Development Program), BK21 FOUR (Brain Korea 21 Phase 4), and the Seoul National University Hospital Research Fund.

□ Introduction to the SNU College of Engineering

Seoul National University (SNU) founded in 1946 is the first national university in South Korea. The College of Engineering at SNU has worked tirelessly to achieve its goal of ‘fostering leaders for global industry and society.’ In 12 departments, 323 internationally recognized full-time professors lead the development of cutting-edge technology in South Korea and serving as a driving force for international development.