P139 - A positive effect on chondrocyte proliferationafter exposure of old murine cartilage in a young systemic enviroment.
Abstract
Purpose
To investigate the effect of an young systemic environment and GDF11 on aging cartilage homeostasis.
Methods and Materials
1. Heterochronic parabiosis model: Group 1, Heterochronic parabiosis ( Y/O); Group 2, Isochronic parabiosis (O/O) ; and Group 3, 12-month-old alone. The knee joints of old mice were examined using X-ray, histology, cell proliferation, immunohistochemistry and qRT-PCR 16 weeks post-surgery. The effect of GDF11 on chondrocytes was observed in vitro by cell proliferation, scratch experiment, and OA-relative-gene expression by Western blot and RT-PCR. In vivo, GDF11 was injected into old mouse joints.The severity of cartilage degeneration were evaluated by histology, immunohistochemistry and qRT-PCR.
Results
1. OARIS score in old mice from the Y/O group was significantly lower compared to O/O and O groups (P<0.05 for both) . The percentage of EdU-positive chondrocytes in old mice from the Y/O group was significantly higher. There was a significant difference in the mRNA expression of collagen type II (Col2) and sex-determining region Y box 9 (Sox9) in old cartilage from the Y/O group compared to those in the O/O and O groups (P<0.05 for both). On the contrary, mRNA expression of runt-related transcription factor 2 (Runx2), collagen type X (Col10), and matrix metalloproteinase 13 (MMP13) in old cartilage from Y/O mice were significantly decreased(P<0.05 for both). The changes in Col2, Col10, MMP13, Runx2 and Sox9 at the protein level mimicked the alterations found at the mRNA level. Similar changes were found in the GDF11 treatment in vitro and in vivo. We further demonstrated that the pSmad2/3 at the protein levels in the GDF11 treated group was higher than in control group.
Conclusion
Young systemic enviroment has a positive effect on chondrocyte proliferation and cartilage matrix synthesis in the old mice. GDF11, one of these young factors involves in the process by up-regulate Smad2/3
