MS/PhD Course Chonnam National University, Republic of Korea
Abstract: Gaucher disease (GD) is a lysosomal storage disorder caused by GBA1 mutations, with ~75% of patients experiencing skeletal complications that significantly impact morbidity and mortality. Understanding the pathophysiological mechanisms underlying GD-related bone abnormalities is crucial for developing effective therapeutic strategies. This study aimed to investigate the roles of osteoblasts and osteoclasts in GD-related skeletal pathology using patient-derived (NC) and GBA1-corrected (COR) cell lines. Osteoblast differentiation, assessed by alkaline phosphatase (ALP) and alizarin red (AR) staining, showed no significant differences between NC and COR, suggesting that osteoblast dysfunction may not be a primary factor in GD-related skeletal abnormalities. However, osteoclast differentiation, evaluated using tartrate-resistant acid phosphatase (TRAP) and F-actin staining, revealed larger and more numerous osteoclasts in NC compared to COR, suggesting that enhanced osteoclast activity may contribute to bone complications in GD. These findings highlight the importance of osteoclast dysregulation in GD-related skeletal pathology. To elucidate the molecular mechanisms underlying osteoclast dysregulation in GD, RNA sequencing (RNA-seq) is needed to identify key regulatory factors. This approach may reveal critical pathways contributing to skeletal pathology and provide potential therapeutic targets. Future research should validate these findings through functional studies to confirm the role of candidate genes in osteoclast differentiation and activity. A deeper understanding of these mechanisms will enhance the potential for novel therapeutic strategies to improve bone health in GD patients.
Funding Source: This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) & funded by the Korean government (MSIT) (No. RS-2023-00261905, 2022M3A9E4017151)
