Retracted: Bone marrow ablation demonstrates that excess endogenous parathyroid hormone plays distinct roles in trabecular and cortical bone.
Mice null for Cyp27b1, which encodes the 25-hydroxyvitamin D-1α-hydroxylase [1α(OH)ase(-/-) mice], lack 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and have hypocalcemia and high parathyroid hormone (PTH) secretion. Intermittent, exogenous PTH is anabolic for bone. To determine the effect of the chronic excess endogenous PTH on osteogenesis and bone turnover, bone marrow ablations (BMX) were performed in tibiae and femurs of 6-week-old 1α(OH)ase(-/-) mice and in wild-type (WT) controls. Newly formed bone tissue was analyzed at 1, 2, and 3 weeks after BMX. BMX did not alter the higher levels of PTH in 1α(OH)ase(-/-) mice. In the marrow cavity, trabecular volume, osteoblast number, alkaline phosphatase-positive areas, type I collagen-positive areas, bone formation-related genes, and protein expression levels all increased significantly after BMX in 1α(OH)ase(-/-) mice, compared with WT. Osteoclast numbers and surface and ratio of RANKL/OPG-relative mRNA levels decreased significantly after BMX in 1α(OH)ase(-/-) mice, compared with WT. In the cortex, alkaline phosphatase-positive osteoblasts and osteoclast numbers increased significantly after BMX in 1α(OH)ase(-/-) mice, compared with WT. These results demonstrate that chronic excess endogenous PTH exerts an anabolic role in trabecular bone by stimulating osteogenic cells and reducing bone resorption, but plays a catabolic role in cortical bone by enhancing bone turnover with an increase in resorption.
Department of Orthopedics, Second Affiliated Hospital of Soochow University, Suzhou, China.
Jun
J
Yan
Weiwei
W
Sun
Jing
J
Zhang
David
D
Goltzman
Dengshun
D
Miao
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D055011:Ablation Techniques; D000818:Animals; D001853:Bone Marrow / Q000502:physiology / Q000601:surgery; D016723:Bone Remodeling / Q000502:physiology*; D001862:Bone Resorption / Q000503:physiopathology; D002118:Calcium / Q000097:blood; D005269:Femur / Q000000981:diagnostic imaging; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology*; D053244:Osteoprotegerin / Q000096:biosynthesis; D010281:Parathyroid Hormone / Q000097:blood / Q000502:physiology*; D010758:Phosphorus / Q000097:blood; D053245:RANK Ligand / Q000096:biosynthesis; D055114:X-Ray Microtomography / Q000379:methods
D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D010758:Phosphorus; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002118:Calcium