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 goal 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.

Effect of X-ray Irradiation on Articular Cartilage Mechanical Properties

“…In terms of cell viability, mature articular cartilage is generally considered as radiation resistant comparative to other tissues with higher proliferative capacity [20,21]. However, being able to degrade various components of the articular matrix, radiation may induce a functional reduction of articular cartilage health after exposure [8].…”

“…Ionizing radiation is known to lower proteoglycan content and compressive stiffness [8,[22][23][24][25]. Previous studies display that reactive oxygen radicals induced by ionizing radiation may be responsible for the degradation of the physiologically important glycosaminoglycan hyaluronan [10,26,27].…”

“…The depth-dependent proteoglycan content affects the cartilage strains substantially. Lowering proteoglycan content in cartilage matrix can thus lessen compressive stiffness, and eventually in the case of continuous growth such a loss can lead towards arthropathies such as osteoarthritis [7,8].…”

“…There is not much data regarding effects of radiation on articular cartilage in the literature, although joint damage has been reported following the cancer treatment or occupational exposures [8]. Most studies on effects of radiation on tissue have concentrated on cells, with less attention paid to the extracellular matrix [10].…”

“…Most studies on effects of radiation on tissue have concentrated on cells, with less attention paid to the extracellular matrix [10]. It has been found that the radiation causes an active degradation of cartilage, through the decline in proteoglycan synthesis, in the human and * e-mail: ekrcicek@gmail.com pig chondrocytes [8]. However, to what level and how the radiation affects the matrix environment has not been studied well yet.…”