【演者】Martin Lotz先生（Professor, The Scripps Research Institute, La Jolla, California）【演題】MULTI-DIMENSIONAL ANALYSIS OF THE HUMAN KNEE AS AN ORGAN TO DISCOVER MECHANISMS OF TISSUE DAMAGE AND PAIN IN OSTEO

第54回システム発生・再生医学分野セミナー ハイブリッド形式にて開催しました

日時：令和7年10月20日（月）17:00-18:00 要旨：Osteoarthritis (OA) is the most prevalent joint disease, with its incidence expected to rise further due to population aging. Despite the identification of numerous drug targets and promising preclinical studies demonstrating efficacy in reducing disease severity, clinical trials for disease-modifying OA drugs have thus far failed, and pain management remains inadequate. These unmet needs stem, in part, from an incomplete understanding of joint biology, aging, and OA pathogenesis. Although the concept of the joint as an organ was proposed years ago, there has yet to be a comprehensive histological, cellular, or molecular study examining all tissues from the same healthy or diseased knees or from other human joints. This project is a whole-joint multiomic analysis to identify novel and more effective therapeutic targets across different stages of joint health deterioration, from early decompensation to end-stage OA progression. Entire knees from organ donors across the age spectrum from healthy donors (age 20-40), intermediate age donors (40-60), aged donors (60-80) in addition to tissues from patients with severe OA undergoing total knee arthroplasty are analyzed from a total of 108 tissue donors. For each tissue including synovium, cartilage, subchondral bone, meniscus and infrapatellar fat pad we performed macroscopic assessment and histopathology as a reference for interpreting omics data. An integrative multiomic analysis profiled all tissues by bulk RNA-sequencing and single nuclei RNA and ATAC-sequencing. We will present transcriptomic patterns at differerent stages of OA and gene regulatory networks and transcription factors in specific cell populations and new therapeutic targets for structure and/or pain modification.

This first whole-joint multiomic analysis provides unprecedented insights into the mechanisms underlying joint aging and OA. By identifying stage-specific and tissue-wide therapeutic targets, this work will inform the development of more effective disease and pain modifying treatments tailored to different stages of OA progression.