TCDD disrupts hypural skeletogenesis during medaka embryonic development.
Defective bone and cartilage development account for a large number of human birth defects annually. Normal skeletogenesis involves cartilage development in early morphogenesis through a highly coordinated and orchestrated series of events involving commitment and differentiation of mesenchymal cells to chondrocytes followed by a highly programmed process of structural maturation. Recent developmental studies with laboratory model fish demonstrate that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in cartilage and skeletal abnormalities. In this study, we exposed embryonic medaka to TCDD to induce developmental modification(s) of both cartilage and bone formation. Emphasis is placed on cell-rich hyaline cartilage of the hypural plate where both chondrogenesis and osteogenesis are impaired by TCDD exposure. In this model, TCDD exposure results in a concentration-dependent impairment of mesenchymal cell recruitment, chondrocyte cell proliferation, differentiation, and progression to hypertrophy. Gene expression of ColA2, a marker of chondrocyte terminal differentiation in hypural structures, is markedly attenuated consistent with hypural dysmorphogenesis. Assessment of hypural structure using a transgenic medaka expressing mCherry under control of the osterix promoter illustrated significant attenuation in expression of the osteoblast gene marker and lack of formation of a calcified perichondral sheath surrounding hypural anlage. Overall, these studies illustrate that TCDD impacts terminal differentiation and growth of cartilage and bone in axial structures not likely derived from neural crest progenitors in medaka hypurals.
Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina 27695, USA.
Wu
W
Dong
David E
DE
Hinton
Seth W
SW
Kullman
D000818:Animals; D002356:Cartilage / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000648:ultrastructure; D024043:Collagen Type II / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009139:Musculoskeletal Abnormalities / Q000139:chemically induced* / Q000196:embryology / Q000473:pathology; D009990:Oryzias / Q000002:abnormalities* / Q000196:embryology; D010012:Osteogenesis / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction
D024043:Collagen Type II; D000072317:Polychlorinated Dibenzodioxins