Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27106, USA.
Int J Radiat Biol. 2013 Apr;89(4):268-77. doi: 10.3109/09553002.2013.747015. Epub 2012 Dec 12.
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.
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.
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.
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.
尽管有报道称癌症治疗或职业暴露后会出现关节损伤,但关于辐射对成人关节(关节)软骨的影响知之甚少。本研究旨在确定辐射是否会减少软骨基质的产生、诱导软骨降解,或干扰 IGF-1 的合成代谢作用。
将单层培养的分离软骨细胞和取自人类供体踝关节和猪膝关节的整个外植体用 2 或 10 Gy γ 射线照射,有或没有 IGF-1 刺激。在第 1 天检查糖胺聚糖合成和 IGF-1 信号;在最初的 96 小时内检查软骨降解情况。
人和猪软骨对辐射的反应相似。细胞活力没有变化。暴露后,基础和 IGF-1 刺激的糖胺聚糖合成减少,尤其是在 10 Gy 后。两种剂量均降低了 IGF 诱导的 Akt 激活和 IGF-1 受体磷酸化。基质金属蛋白酶(ADAMTS5、MMP-1 和 MMP-13)和糖胺聚糖在 2 和 10 Gy 后释放到培养基中。
辐射诱导软骨主动降解,减少糖胺聚糖合成,并损害人和猪软骨细胞中的 IGF-1 信号。降低的 Akt 激活可能是基质合成减少的原因。辐射可能会导致关节暴露后软骨健康功能下降,导致关节病。