Ionizing radiation causes active degradation and reduces matrix synthesis in articular cartilage

Abstract

Purpose: Little is known regarding radiation effects on adult articular (joint) cartilage, though joint damage has been reported following cancer treatment or occupational exposures. The aim of this study was to determine if radiation can reduce cartilage matrix production, induce cartilage degradation, or interfere with the anabolic effects of IGF-1.

Materials and methods: Isolated chondrocytes cultured in monolayers and whole explants harvested from ankles of human donors and knees of pigs were irradiated with 2 or 10 Gy γ-rays, with or without IGF-1 stimulation. Proteoglycan synthesis and IGF-1 signaling were examined at Day 1; cartilage degradation throughout the first 96 hours.

Results: Human and pig cartilage responded similarly to radiation. Cell viability was unchanged. Basal and IGF-1 stimulated proteoglycan synthesis was reduced following exposure, particularly following 10 Gy. Both doses decreased IGF-induced Akt activation and IGF-1 receptor phosphorylation. Matrix metalloproteinases (ADAMTS5, MMP-1, and MMP-13) and proteoglycans were released into media after 2 and 10 Gy.

Conclusions: Radiation induced an active degradation of cartilage, reduced proteoglycan synthesis, and impaired IGF-1 signaling in human and pig chondrocytes. Lowered Akt activation could account for decreased matrix synthesis. Radiation may cause a functional decline of cartilage health in joints after exposure, contributing to arthropathy.

Keywords::

• Radiation
• chondrocyte
• cartilage
• IGF-1
• arthritis

Acknowledgements

The authors would like to acknowledge Dr James E. Jordan in the Department of Cardiothoracic Surgery and Dr Michael J. Morykwas in the Department of Plastic and Reconstructive Surgery at Wake Forest University School of Medicine for graciously donating pig tissue. We would also like to thank Meredith Greene, Mary Zhao, and Uma Ghandi for technical assistance, Dr Raghunatha Yammani for helpful discussions, and Elizabeth Moore and Valerie Payne for help with all irradiations.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This project was supported by the National Institutes of Health (T32 CA113267 JSW; R01AG016697 RFL).