TGF-β Stimulates Endochondral Differentiation after Denervation

Transforming growth factor beta (TGF-β) is a multifunctional protein that induces gene expression of cartilage-specific molecules, but its exact role in the process of chondrogenesis is unclear. Because recent studies suggest that TGF-β can facilitate chondrogenic precursor cells differentiating into chondrocytes, we sought to determine whether TGF-β prevents denervation-induced reduction of endochondral bone formation in an experimental model. Mice were treated daily with recombinant human TGF-β1 (rhTGF-β1) for 3 weeks. We found that rhTGF-β1 not only prevented denervation-induced reduction of gene expression of type II collagen, type X collagen, aggrecan, Indian hedgehog, and parathyroid hormone-related peptide, but also synergized endochondral differentiation. These results demonstrate that short-term systemic administration of TGF-β substantially prevents denervation-induced reduction of endochondral bone formation via stimulating endochondral differentiation. Potential therapeutic applications will be pursued in further studies that address the molecular biological mechanism of TGF-β on endochodral bone formation after denervation in animal models.