Tendons are robust structures, made of cellular and extracellular components, that transmit force efficiently between muscle and bone that is essential for permitting strength and mobility in vertebrates. Although the tendon is mainly comprised of extracellular matrix, resident tendon cells – tenoblasts and tenocytes – have been established as responsible for constructing the fibrotic structure of the tendon during development.
Various forms of tendinopathy impact a broad demographic range, yet effective treatment modalities remain rather limited due to our lack of understanding of the molecular mechanisms that drive tendon healing, which has made this a critical area of tendon research. Recently, the presence of a stem cell/progenitor-like tendon cell population within the tendon was identified, implicating their potential role in tendon regeneration and providing course for further research on this novel tendon cell population (Bi et al., 2007) .
Several genetic markers, such as Scleraxis (Scx), collagen type I (Col I) and Mohawk (Mkx), have been shown to trace the tendon cell lineage (Edom‐Vovard & Duprez, 2004; Ito et al., 2010; Schweitzer et al., 2001). However, they do not provide specificity towards these tendon-derived stem cell/progenitor cells (TSPCs), nor do they give much insight into the interactions between the resident cells that govern tendon biology. Through the use of an Axin2 marker, previous stem cell research has suggested the Wnt/beta-Catenin signaling pathway to be involved in regulating the self-renewing capacity of these cells within the intestine, liver, epidermis and brain (Bowman, van Amerongen, Palmer, & Nusse, 2013; Lim et al., 2013; Wang, Zhao, Fish, Logan, & Nusse, 2015). Therefore, this study aims to apply the Axin2 marker to the previously identified TSPC population to illustrate the heterogeneity of these cells and implicate that their proliferative potential is controlled through Wnt/beta-Catenin signaling.
By using an Axin2-CreERt2;Rosa-LSLTdTomato mouse model in an injured state, due to the disruption of the tendon matrix during TSPC isolation, we have demonstrated through RT-qPCR analysis that there are differences in gene expression between Axin2+/- cells, particularly in Mkx and Col II. Furthermore, we utilized cell counting and FACS analysis to show that the Axin2+ cells have a greater propensity to proliferate than Axin2- cells. Our findings suggest that the Wnt/beta-Catenin pathway is involved in regulating tendon cell fate and may be an underlying mechanism behind tendon repair.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/36556 |
| Date | 12 June 2019 |
| Creators | Green, Joshua Solomon |
| Contributors | Mostoslavsky, Gustavo |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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