Killing Two Birds with One Stone: Early Detection of Osteoporosis and Real-Timing Monitoring of Therapeutic Effects
Opening a new horizon for real-time imaging of osteoclasts, the major cause of pathogenic bone destruction, and for bone disease research
The research results from the research team of Professor Kim Jong Seung and Professor Park Serk In were published in a main cover article of Angewandte Chemie, an internationally renowned journal.

  ▲ (From left) Professor Koo Seyoung (first author, Hyupsung University), Postdoc Researcher Lee Eun Jung (first author, KU),
    Professor Park Serk In (corresponding author, KU), and Professor Kim Jong Seung (corresponding author, KU).

The research team led by Professor Kim Jong Seung and Professor Park Serk In of KU developed an innovative two-photon fluorogenic probe that can be used for early diagnosis of the risk of osteoporosis and molecular monitoring of the treatment process, presenting a new paradigm of bone disease study and treatment.

Their report entitled “Real-Time Live Imaging of Osteoclast Activation via Cathepsin K Activity in Bone Diseases” was published on February 5 in  Angewandte Chemie  International Edition (IF: 16.823), which is a globally renowned journal in chemistry published by the German Society of Chemistry. Since the research was evaluated to be a giant step forward for the study and treatment of bone diseases, the article was chosen as the main cover article of the issue.

Osteoporosis, characterized by a decrease in bone mass and coarse bone tissue due to changes in the microstructure, is a disease that can easily lead to fractures resulting from even small impacts. The prevalence of osteoporosis in Korea over the age of 50 is 22.4%, and it is a disease that commonly occurs due to aging. However, since there are no particular physical symptoms until a fracture occurs, it is necessary to determine the risk of osteoporosis early and prevent bone loss. Currently, bone density testing using X-rays and blood bone marker testing are carried out to diagnose the risk of osteoporosis in a basic way, but these methods are unable to detect the direct causes of the decrease in bone mass. Thus, the conventional testing methods are limited in both accurately determining the risk of osteoporosis and monitoring the treatment process.

The joint research team led by Professor Kim Jong Seung of the Department of Chemistry of the College of Science and Professor Park Serk In of the Department of Biochemistry and Molecular Biology of the College of Medicine paid attention to the overactivation of osteoclasts, one of the direct causes of bone mass loss, and based on this presented a novel method of assessing decrease in bone mass.

Osteoclasts, one of the main cells making up bones, maintain the shape and strength of bone tissues through the bone resorption process and play an important physiological function in repairing damaged bones. However, in pathological conditions, overactivated osteoclasts cause indiscriminate bone destruction, which causes various bone diseases, such as osteoporosis, rheumatism, and arthritis. The joint research team focused on the cathepsin K enzyme that is secreted by osteoclasts during the bone resorption process and developed a two-photon fluorogenic probe to detect it, successfully performing real-time observation of the activity of osteoclasts.

▲ February 2024 Issue Cover Image of Angew. Chem. Int. Ed.
(DOI: doi.org/10.1002/anie.202318459)

The fluorogenic probe, newly developed by the research group, was used for real-time tracking of the osteoclast activity in murine models of excessive osteoclastogenesis, osteoporosis, and bone metastasis. In addition, it was used for the early diagnosis of a higher risk of bone density loss than the control group. Furthermore, the research team performed a real-time observation of the decrease in osteoclast activity following the administration of a drug for inhibiting decreases in bone mass. They thereby demonstrated that the probe can be employed as an effective assessment tool in the treatment of osteoporosis.

Professor Kim and Professor Park said, “The fluorogenic probe for cathepsin K detection that we developed in our study represents substantial progress in the early diagnosis of osteoporosis risk and in treatment monitoring.” They added, “We look forward to providing a new breakthrough in understanding the mechanisms of bone diseases and developing treatment strategies.”

The research was supported by the National Research Foundation of Korea funded by the Ministry of Science and ICT and the Ministry of Education.