P114 - Short-Term Response of Human Meniscus Model to Simulated Microgravity
- Z. Ma (Edmonton, CA)
- Z. Ma (Edmonton, CA)
- D. Li (Edmonton, CA)
- M. Kunze (Edmonton, CA)
- A. Mulet-Sierra (Edmonton, CA)
- L. Westover (Edmonton, CA)
- A. Adesida (Edmonton, CA)
Abstract
Purpose
Osteoarthritis (OA) is a degenerative disease with much of the focus on knee OA (KOA). As the crucial load-bearing structure, the meniscus is a potential contributor to KOA. The molecular mechanisms regulating the pathogenesis of KOA are poorly understood. However, some characteristics of meniscus fibrochondrocytes (MFCs) from KOA resemble hypertrophic articular chondrocytes undergoing endochondral ossification. We discovered previously that simulated microgravity (SMG) upregulated the expression of hypertrophic markers (COL10A1 and MMP13) of meniscus models developed from human MFCs over several weeks. But the short-term effect was not explored. The aim of this study is to investigate the short-term gene expression profile of human meniscus models exposed to SMG.
Methods and Materials
Human meniscus specimens were procured from 5 males with no history of KOA. Meniscus models were constructed with isolated primary MFCs. The engineered models were cultured under static gravity and SMG conditions for 7 days. Scaffolds were harvested on day 0, 1, 3, and 7, and the expression levels of selected markers were measured by RT-qPCR.
Results
The expression level of the chondrogenic transcription factor SOX9 was comparable in the SMG and static groups on day 1. With prolonged culture, a decrease of expression level in SMG compared to static control was observed. On day 7, SOX9 expression level was 2.2-fold lower. A similar pattern was detected for chondrogenic marker aggrecan (ACAN) and type II collagen (COL2A1). The expression levels were approximately 3-fold lower in the SMG group for both markers on day 7. On the contrary, hypertrophic maker expression level showed continuous upregulation by SMG. On day 7, the type X collagen (COL10A1), matrix metalloproteinase (MMP13), and Indian Hedgehog (IHH) expression levels increased by 1.4-fold, 4.6-fold, and 2.2-fold by SMG, respectively.
Conclusion
Short-term exposure of meniscus models derived from primary human MFCs to SMG resulted in OA-like gene expression profiles.