PTHrP/IHH Involvement in TGF beta and Bone Morphogenic Protein Cross-Talk in the Growth Plate and In Vitro Cartilage Development to Prevent Hypertrophy of Mesenchymal Stromal/Stem Cells

摘要

Mesenchymal stem/stromal cells (MSCs) serve as a promising candidate for tissue engineering-based cartilage regeneration therapy because of their availability and multipotent capacity. However, premature hypertrophy is the main obstacle to the routine application of MSCs in the generation of stable cartilage. Transforming growth factor-beta (TGF beta) is an anti-hypertrophy signal, whereas bone morphogenic proteins (BMPs) have the opposite effect on bone formation. In addition, the parathyroid hormone-related protein (PTHrP)/Indian hedgehog (IHH) signaling pathway is recognized as the most powerful pathway mediating chondrocyte hypertrophy. Understanding the cross-talk between TGF beta, BMPs and PTHrP/IHH may thus provide insight to eliminate this undesirable phenomenon. This review elucidates these interactions during bone formation and compares them with those observed during MSCs hypertrophic processes in vitro, with the aim of facilitating cell-based regeneration of functional and stable cartilage.