Abstract
In the past 3 decades, the cartilage repair potential of mesenchymal stromal cells, or mesenchymal stem cells (MSCs), has been widely examined in animal studies. Unfortunately, the phenotype and physical properties of MSC-derived cartilage tissue are not comparable to native hyaline cartilage. In particular, chondrocytic hypertrophy, a phenotype that is not observed in healthy hyaline cartilage, is concomitant with MSC chondrogenesis. Given that hypertrophic chondrocytes potentially undergo apoptosis or convert into osteoblasts, this undesired phenotype needs to be prevented or minimized before MSCs can be used to repair cartilage injuries in the clinic. In this review, we first provide an overview of chondrocytic hypertrophy and briefly summarize current methods for suppressing hypertrophy in MSC-derived cartilage. We then highlight recent progress on modulating the canonical Wnt/β-catenin pathway for inhibiting hypertrophy. Specially, we discuss the potential crosstalk between Wnt/β-catenin with other pathways in regulating hypertrophy. Lastly, we explore future perspectives to further understand the role of Wnt/β-catenin in chondrocytic hypertrophy.
Highlights
Articular cartilage, an essential component of the joint organ, helps maintain stability, distribute force and reduce friction during physical activity
These cells remodel the matrix to support osteogenesis, which is mainly characterized by the expression of runt-related transcription factor 2 (RUNX2), matrix metalloproteinase (MMP)-13, COL10, alkaline phosphatase (ALP) and osteogenic growth factors, such as bone morphogenetic protein (BMPs), Indian hedgehog (IHH), and vascular endothelial growth factor (VEGF) among others (Sun and Beier, 2014)
When mesenchymal stem cells (MSCs) are induced to undergo chondrogenesis with medium containing transforming growth factor (TGF-β), the newly formed cartilage recapitulates many features observed in hypertrophic chondrocytes in bone development, such as large cell size and high expression of hypertrophy-relevant markers (Chen et al, 2015) (Figures 1B,C)
Summary
An essential component of the joint organ, helps maintain stability, distribute force and reduce friction during physical activity. Some clinical trials have shown the potential of MSC-based cartilage tissue engineering in the repair of chondral defects in humans (Gupta et al, 2016; Park et al, 2017; Qiao et al, 2020), but a greater sample size is required to confirm the reparative results and phenotype of newly formed cartilage In spite of this exciting progress, extensive in vitro data and animal studies have shown that MSC-derived cartilage does not fully recapitulate the structure or composition of hyaline cartilage matrix (Bian et al, 2013; Watts et al, 2013; Yang et al, 2018). We discuss the crosstalk between Wnt/β-catenin and other pathways in regulating hypertrophy
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