Low-dose irradiation could mitigate osteoarthritis progression by modulating mitochondrial function
Byoung Hyuck Kim,
Korea Republic of
PO-1911
Abstract
Low-dose irradiation could mitigate osteoarthritis progression by modulating mitochondrial function
Authors: Byoung Hyuck Kim1, Hyun Cheol Bae2, Jeanny Kwon3, Hyuk-Soo Han2, Hak Jae Kim4
1Seoul Metropolitan Government Seoul National University Boramae Medical Center, Radiation Oncology, Seoul, Korea Republic of; 2Seoul National University College of Medicine, Orthopaedic Surgery, Seoul, Korea Republic of; 3Chungnam National University School of Medicine, Radiation Oncology, Daejeon, Korea Republic of; 4Seoul National University College of Medicine, Radiation Oncology, Seoul, Korea Republic of
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Purpose or Objective
The use of low-dose radiation therapy (LDRT) for
osteoarthritis (OA) are rarely implemented except some European regions. There
is a controversy over its clinical effects whereas little is known about how
LDRT affects the actual disease progression.
Material and Methods
Using primary cultured human chondrocytes and
synovium-derived cells from OA patients, the effects of LDRT were measured by
cell viability assay, quantitative real-time PCR, western blotting, and RNA
sequencing. For in vivo validation, a surgically induced OA model was used.
Results
In vitro experiments indicated that LDRT have no
significant impact on cell death, but slightly decreased expressions of
pro-inflammatory factors including MMP13, without change in chondrogenesis
markers. LDRT induces large transcriptomic changes in these cells, especially
in mitochondrial activities. Growth differentiation factor 15 (GDF15) which is
a mitohormetic signaling factor increased after LDRT and seemed to mediate
anti-inflammatory effects of LDRT. We next found that rats treated with LDRT after
anterior cruciate ligament transection or surgical destabilization of the
medial meniscus exhibited decreased severity of OA compared to no-irradiation
group at 10 weeks after surgery (mean OARSI score 3.7 in 0 Gy, 2.8 in 0.5 Gy,
and 1.8 in 1 Gy, p = 0.003). The osteoclast activity also appeared to be
significantly reduced in the LDRT group.
Conclusion
Taken together, LDRT could mitigate osteoarthritis
progression by exerting its anti-inflammatory effects through modulating
mitochondrial function.