title: Low-dose X-ray irradiation promotes osteoblast proliferation, differentiation and fracture healing.
abstract: Great controversy exists regarding the biologic responses of osteoblasts to X-ray irradiation, and the mechanisms are poorly understood. In this study, the biological effects of low-dose radiation on stimulating osteoblast proliferation, differentiation and fracture healing were identified using in vitro cell culture and in vivo animal studies. First, low-dose (0.5 Gy) X-ray irradiation induced the cell viability and proliferation of MC3T3-E1 cells. However, high-dose (5 Gy) X-ray irradiation inhibited the viability and proliferation of osteoblasts. In addition, dynamic variations in osteoblast differentiation markers, including type I collagen, alkaline phosphatase, Runx2, Osterix and osteocalcin, were observed after both low-dose and high-dose irradiation by Western blot analysis. Second, fracture healing was evaluated via histology and gene expression after single-dose X-ray irradiation, and low-dose X-ray irradiation accelerates fracture healing of closed femoral fractures in rats. In low-dose X-ray irradiated fractures, an increase in proliferating cell nuclear antigen (PCNA)-positive cells, cartilage formation and fracture calluses was observed. In addition, we observed more rapid completion of endochondral and intramembranous ossification, which was accompanied by altered expression of genes involved in bone remodeling and fracture callus mineralization. Although the expression level of several osteoblast differentiation genes was increased in the fracture calluses of high-dose irradiated rats, the callus formation and fracture union were delayed compared with the control and low-dose irradiated fractures. These results reveal beneficial effects of low-dose irradiation, including the stimulation of osteoblast proliferation, differentiation and fracture healing, and highlight its potential translational application in novel therapies against bone-related diseases.
authors.affiliation: Department of Orthopedics, Shaanxi Provincial Peoples Hospital, Xi'an, Shaanxi, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Chang
authors.initials: C
authors.lastname: She
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Zong-Gang
authors.initials: ZG
authors.lastname: Xie
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Yong-Tao
authors.initials: YT
authors.lastname: Mao
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Qi-Rong
authors.initials: QR
authors.lastname: Dong
authors.affiliation: Department of Orthopedics, Shaanxi Provincial Peoples Hospital, Xi'an, Shaanxi, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ling
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001861:Bone Regeneration / Q000502:physiology / Q000528:radiation effects*; D002454:Cell Differentiation / Q000528:radiation effects; D002460:Cell Line; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005264:Femoral Fractures / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D005269:Femur / Q000293:injuries / Q000378:metabolism / Q000528:radiation effects*; D017102:Fracture Healing / Q000502:physiology / Q000528:radiation effects*; D015870:Gene Expression; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014965:X-Rays
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D018809:Proliferating Cell Nuclear Antigen; C493717:Runx2 protein, rat; C495181:Sp7 protein, rat; D014157:Transcription Factors; D015675:Osteocalcin; D000469:Alkaline Phosphatase
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