Positive Effects of a Young Systemic Environment and High Growth Differentiation Factor 11 Levels on Chondrocyte Proliferation and Cartilage Matrix Synthesis in Old Mice.

Objective: To investigate the effects of a young systemic environment and growth differentiation factor 11 (GDF‐11) on aging cartilage. Methods: A heterochronic parabiosis model (2‐month‐old mouse and 12‐month‐old mouse [Y/O]), an isochronic parabiosis model (12‐month‐old mouse and 12‐month‐old mouse [O/O]), and 12‐month‐old mice alone (O) were evaluated. Knee joints and chondrocytes from old mice were examined by radiography, histology, cell proliferation assays, immunohistochemistry, Western blotting, and quantitative reverse transcriptase–polymerase chain reaction 16 weeks after parabiosis surgery. GDF‐11 was injected into 12‐month‐old mouse joints daily for 16 weeks. Cartilage degeneration, cell proliferation, and osteoarthritis‐related gene expression were evaluated. Results: Osteoarthritis Research Society International scores in old mice were significantly lower in the Y/O group than in the O/O and O groups (both P < 0.05). The percentage of 5‐ethynyl‐2′‐deoxyuridine–positive chondrocytes in old mice was significantly higher in the Y/O group than in the other groups (P < 0.05). Type II collagen (CII) and SOX9 messenger RNA levels differed in cartilage from old mice in the Y/O group compared to the O/O and O groups (both P < 0.05). RUNX‐2, CX, and matrix metalloproteinase 13 levels were significantly lower in cartilage from old mice in the Y/O group compared to the O/O and O groups (both P < 0.05). Similar results were obtained for protein expression levels and after GDF‐11 treatment in vitro and in vivo. Phosphorylated Smad2/3 (pSmad2/3) levels were higher in the recombinant GDF‐11–treated group than in the control group. Conclusion: A young systemic environment promotes chondrocyte proliferation and cartilage matrix synthesis in old mice. GDF‐11, a "young factor," contributes to these effects through the up‐regulation of pSmad2/3. [ABSTRACT FROM AUTHOR]