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A Lab-On-A-Chip Platform for Stimulating Osteocyte Mechanotransduction and Analyzing Functional Outcomes of Bone Remodeling
Published on: May 21, 2020
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Novel in vitro microfluidic platform for osteocyte mechanotransduction studies
Liangcheng Xu1, Xin Song1, Gwennyth Carroll1
1Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Summary
This study developed a microfluidic device to investigate how osteocytes (bone cells) respond to mechanical stress and influence osteoclast (bone-resorbing cells) activity. Findings show mechanical stress on osteocytes impacts osteoclast differentiation, offering insights into bone remodeling and potential drug targets.
Area of Science:
- Biotechnology
- Cell Biology
- Biomaterials
Background:
- Osteocytes are key mechanosensors in bone remodeling.
- Current in vitro models lack the physiological relevance of microfluidic systems.
- Understanding osteocyte-osteoclast interactions is crucial for bone health.
Purpose of the Study:
- To design and fabricate a multi-shear stress microfluidic co-culture platform.
- To investigate the interaction between osteocytes and osteoclasts under varying flow conditions.
- To explore the impact of mechanical stress on osteocyte-osteoclast signaling.
Main Methods:
- Fabrication of a polydimethylsiloxane (PDMS)-based microfluidic device using soft lithography.
- Co-culture of osteocytes and osteoclasts in adjacent channels connected by perfusion channels.
- Application of varying shear stress levels to osteocyte channels.
- Analysis of RANKL levels and osteoclast differentiation.
Main Results:
- Significant differences in RANKL levels were observed under varying shear stress.
- Osteocyte mechanotransduction directly affected pre-osteoclast differentiation.
- Increased shear stress on osteocytes led to decreased osteoclast differentiation.
- Zoledronic acid further reduced osteoclast differentiation, compounding shear stress effects.
Conclusions:
- The novel microfluidic platform effectively mimics in vitro bone interstitial fluid flow and cell interactions.
- Mechanically stimulated osteocytes modulate osteoclast differentiation.
- This platform is valuable for bone cell mechanistic studies and identifying drug targets for bone diseases.
