title: Early-stage pathogenic sequence of jaw osteoradionecrosis in vivo.
abstract: The mechanism underlying jaw osteoradionecrosis (ORN) is not fully understood, particularly in the early stages. To investigate bone and vessel pathogenesis in the early stages of jaw ORN, we generated a mandibular ORN model in miniature pigs (minipigs) by applying a combination of single-dose 25-Gy irradiation (IR) and tooth extraction. We studied 6 ORN model minipigs and 6 control, non-irradiated minipigs. We measured dynamic morphological changes, bone-remodeling-associated gene expression, sphingomyelinase activity, and local blood flow. Bone remodeling, including bone resorption and new bone formation, was observed within 15 days post-IR. Later, an ORN-related imbalance in bone metabolism gradually occurred, with loss of bone regeneration capacity, collagen collapse, and microvascular obliteration. Within 24 hrs post-IR, sphingomyelinase significantly increased in irradiated tissues. At 1 wk post-IR, local blood flow increased, but at 15 days post-IR, it significantly decreased to 50% below normal levels. This study provided details of the sequential occurrences in early-stage ORN in a large animal model. Our results suggested that reduced local blood flow and consequent hypovascularity may have caused an imbalance in bone remodeling. This suggested that microvessel damage may play a key role in the initiation of ORN.
authors.affiliation: Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, P. R. China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: Z
authors.initials: Z
authors.lastname: Zheng
authors.forename: D
authors.initials: D
authors.lastname: Fang
authors.forename: R
authors.initials: R
authors.lastname: Gao
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: Z P
authors.initials: ZP
authors.lastname: Fan
authors.forename: C M
authors.initials: CM
authors.lastname: Zhang
authors.forename: S L
authors.initials: SL
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001861:Bone Regeneration / Q000528:radiation effects; D016371:Cranial Irradiation / Q000009:adverse effects*; D020287:In Situ Nick-End Labeling; D008334:Mandible / Q000098:blood supply / Q000528:radiation effects; D008336:Mandibular Diseases / Q000201:enzymology / Q000473:pathology*; D055806:Microvessels / Q000528:radiation effects; D010025:Osteoradionecrosis / Q000201:enzymology / Q000473:pathology*; D011897:Random Allocation; D012039:Regional Blood Flow / Q000528:radiation effects; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature
chemical_list: D013108:Sphingomyelin Phosphodiesterase