机构:[1]Department of Orthopedics,Second Affiliated Hospital of Soochow University, Suzhou, China[2]the State Key Laboratory of Reproductive Medicine,the Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China[3]the Department of Medicine, McGill University, Montreal, Quebec, Canada
Mice null for Cyp27b1, which encodes the 25-hydroxyvitamin D-1 alpha-hydroxylase [1 alpha(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 1 alpha(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 1 alpha(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 1 alpha(OH)ase(-/-) mice, compared with WT. Osteoclast numbers and surface and ratio of RANKL/OPG-relative mRNA levels decreased significantly after BMX in 1 alpha(OH)ase(-/-) mice, compared with WT. In the cortex, alkaline phosphatase-positive osteoblasts and osteoclast numbers increased significantly after BMX in 1 alpha(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. (Am J Pathol 2012, 181:234-244; http://dx.doi.org/10.1016/j.ajpath.2012.03.038)
基金:
Supported by a Key Project grant from the National Natural Science
Foundation of China (30830103), by the National Basic Research Program
of China (2012CB966902 to D.M.), and by a grant from the Canadian
Institutes for Health Research (D.G.).
第一作者机构:[1]Department of Orthopedics,Second Affiliated Hospital of Soochow University, Suzhou, China
共同第一作者:
通讯作者:
通讯机构:[*]State Key Laboratory of Reproductive Medicine, Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
推荐引用方式(GB/T 7714):
Jun Yan,Weiwei Sun,Jing Zhang,et al.Bone Marrow Ablation Demonstrates That Excess Endogenous Parathyroid Hormone Plays Distinct Roles in Trabecular and Cortical Bone[J].AMERICAN JOURNAL OF PATHOLOGY.2012,181(1):234-44.doi:10.1016/j.ajpath.2012.03.038.
APA:
Jun Yan,Weiwei Sun,Jing Zhang,David Goltzman&Dengshun Miao.(2012).Bone Marrow Ablation Demonstrates That Excess Endogenous Parathyroid Hormone Plays Distinct Roles in Trabecular and Cortical Bone.AMERICAN JOURNAL OF PATHOLOGY,181,(1)
MLA:
Jun Yan,et al."Bone Marrow Ablation Demonstrates That Excess Endogenous Parathyroid Hormone Plays Distinct Roles in Trabecular and Cortical Bone".AMERICAN JOURNAL OF PATHOLOGY 181..1(2012):234-44