MPhil Student The University of Hong Kong Tseung Kwan O, Hong Kong
Abstract: The adult human skeleton is constantly renewed in a process called remodeling, which is essential for maintaining healthy bones. However, up to one in three people, both young and old, suffer from issues related to abnormal bone mass. Osteogenesis Imperfecta (OI) is a rare group of diseases that result in fragile bones that break easily. Traditionally, OI is treated with drugs and hormones, but these treatments can lead to problems like unusual fractures or bone death over time, and although they may increase bone density, the bone quality often remains poor.
Researchers have looked into using mesenchymal stem cell (MSC) transplants as a long-term treatment for OI, but the benefits observed in clinical trials were only short-term. Recently, unique skeletal stem cells (SSCs) were identified that may be more preferable for bone regeneration. These SSCs are found in certain parts of long bones in both mice and humans. SSCs are very rare among the broader family of MSCs, which may explain why MSC transplants haven't been very effective in the long run.
Our lab has created a mouse model, (13del-tg) where a mutant form of Collagen X causes ER-stress in osteocytes, impairing maturation and the expression of Sclerostin (SOST), resulting in excessive bone growth, of both the periosteal and endosteal origin. To understand how SSCs from the bone marrow contribute to endosteal bone growth, we assessed SSCs in various bone regions using flow cytometry and single cell transcriptomics.
Further, we showed that these SSCs are in close association with blood vessels in the bone marrow. We propose that in 13del mice, there may be a mechanism of enhanced recruitment and/or differentiation of SSCs on the inner bone surface that promoting bone growth. This population of SSCs could be candidate for cell therapy in patients with OI, and we plan to test this in an OI mouse model.
Funding Source: Hong Kong Health Bureau - Health and Medical Research Fund
