1. School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China;
2. Department of Neurology, University of Chicago, Chicago, IL, USA;
3. Department of Epidemiology and Biostatistics & Guangdong Key Lab of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangdong, China;
4. Department of Biology, University of Pacifica, Stockton, CA, USA.
# First two authors have equal contribution in this work.
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.
Keywords: TGF-β1, denervation, endochondral differentiation, ColII, ColX, aggrecan.