Investigating Osteoblast-Osteoclast Coupling: Chemical Modulation and Implications for Bone Formation – UROP Spring Symposium 2025

Investigating Osteoblast-Osteoclast Coupling: Chemical Modulation and Implications for Bone Formation

Christina Huerta-Stylianou

Research Mentor(s): Yuji Mishina
Mentor Department: Biological and Material Sciences
Authors: Susannah Midla, Yuji Mishina
Session: Session 5 (2:00pm – 2:50pm)
Presentation Type: Poster 24

Abstract

The human bone is a dynamic organ that serves as the structural foundation of the body and is more than just a framework. Osteoblasts (OB) are bone forming cells and osteoclasts (OCLs) are bone resorption cells. OB-OCL coupling is a crucial mechanism that maintains bone mass through a balanced process of bone formation and resorption, playing a key role in bone homeostasis. However, the communication between OBs and OCLs is still being fully understood. In this project, we researched this mechanism to better understand its complexities and potential therapeutic implications. Previous studies have shown that OBs and OCLs communicate through multiple mechanisms, including direct cell-to-cell contact and soluble signaling molecules. Direct communication has been identified as a mechanism to decrease osteoblast activity. We previously found that Cytochalasin D treatment that blocks direct communication enhances bone mass by promoting osteoblast activity in calvarial ex vivo cultures. However, Cytochalasin D is also toxic and nonspecific. This study aimed to examine OB-OCL communication through multiple experimental approaches, incorporating various culture models and chemical treatments to assess their effects on cellular interactions. Our goal was to use safer chemicals with high specificity to target direct cell-cell communication to upregulate bone formation. Several chemicals, including Prednisone, Darunavir, Edaravone, and Flunixin Meglumine, were selected based on their potential relevance to OB and OCL biology. It is expected that these chemicals augment bone formation in co-culture due to restricted direct communication. Future research will be to use the chemical treatment with the highest promotion of osteoblast activity on in-house wildtype mice to observe in vivo effects on bone density and structure. We will additionally repeat this experiment using osteoporosis model mice to investigate the impact of altered OB-OCL communication, aiming to explore therapeutic interventions for improving bone health in conditions of osteoporotic degeneration.

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