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Pinealectomy in a broiler chicken model impairs endochondral ossification and induces rapid cancellous bone loss
Authors:Yoichi Aota  Hayato Terayama  Tomoyuki Saito  Masahiro Itoh
Affiliation:1. Research Service, Veterans Affairs Palo Alto Health Care System (VAPAHCS), Palo Alto, California, USA;2. Renal Division, Department of Medicine, Stanford University, Stanford, California, USA;1. Douglas Stephens Surgical Research Laboratory, Murdoch Children’s Research Institute, Melbourne, Australia;2. Urology Department, Royal Children''s Hospital, Melbourne, Australia;3. Department of Paediatrics, University of Melbourne, Australia;4. Division of Developmental Biology, Cincinnati Children''s Hospital Research Foundation
Abstract:
Background contextAdolescent idiopathic scoliosis (AIS) in humans is a lateral curvature of the spine often associated with osteopenia. It has recently been accepted that the development of AIS is closely associated with spinal overgrowth. Pinealectomy (PNX) in a chicken model consistently induces scoliosis with anatomic features similar to human AIS; however, the mechanism of PNX inducing scoliosis is poorly understood.PurposeThis experimental study attempts to improve the understanding of the mechanisms underlying the onset of scoliosis in a PNX broiler chicken model.MethodsA histomorphometric study was performed to analyze longitudinal bone growth and cancellous bone remodeling before the development of scoliosis. Static and dynamic parameters in cancellous bone and chondro-osseous junction of the 7th thoracic vertebral body at 9 days after hatching were compared between PNX chickens (n=9) and control chickens with no surgery (n=5).ResultsPNX resulted in a rapid and marked loss of cancellous bone volume (7.9±0.9% vs. 14.2±1.8%, mean±SD, p<.0005) and profoundly disrupted trabecular structure with increases in dynamic formative parameters, such as mineralizing surface, mineralization apposition rate, and adjusted appositional rate. In the chondro-osseous junction, activated osteoclasts phagocytized degenerating chondrocytes, leaving a minimal amount of cartilage matrix and activated osteoblasts, losing their scaffolding for bone formation, and directly covering the hypertrophic zone cells. The osteoid surface and thickness in the chondro-osseous junction were significantly increased in PNX chickens (43.1±14.2% vs. 11.6±5.7% and 4.1±0.2μm vs. 2.9±0.4 μm). In the subjacent cartilage regions being protected from further resorption, abundant labeled cartilage remained with higher cellularity.ConclusionsIt is known that fast-growing birds have a unique paradigm of rapid bone elongation with minimal metaphyseal bone production. A bone-forming surface exists at the front of cartilage ossification in the growth plate; therefore, papillae of hypertrophic chondrocytes become included between the trabeculae of metaphyseal bone and the overall thickness of the growth plate increases considerably in addition to distal expansion. Our results indicate that the unique mechanism for rapid bone elongation in chicken is more pronounced after PNX. PNX also induces high turnover osteoporosis, which may also contribute to the development of scoliosis in the chicken.
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