Synergistic effects of high dietary calcium and exogenous parathyroid hormone in promoting osteoblastic bone formation in mice.
In the present study, we investigated whether high dietary Ca and exogenous parathyroid hormone 1-34 fragments (PTH 1-34) have synergistic effects on bone formation in adult mice, and explored the related mechanisms. Adult male mice were fed a normal diet, a high-Ca diet, a PTH-treated diet, or a high-Ca diet combined with subcutaneously injected PTH 1-34 (80 μg/kg per d) for 4 weeks. Bone mineral density, trabecular bone volume, osteoblast number, alkaline phosphatase (ALP)- and type I collagen-positive areas, and the expression levels of osteoblastic bone formation-related genes and proteins were increased significantly in mice fed the high-Ca diet, the PTH-treated diet, and, even more dramatically, the high-Ca diet combined with PTH. Osteoclast number and surface and the ratio of receptor activator for nuclear factor-κB ligand (RANKL):osteoprotegerin (OPG) were decreased in the high-Ca diet treatment group, increased in the PTH treatment group, but not in the combined treatment group. Furthermore, third-passage osteoblasts were treated with high Ca (5 mM), PTH 1-34 (10⁻⁸ M) or high Ca combined with PTH 1-34. Osteoblast viability and ALP activity were increased in either the high Ca-treated or PTH-treated cultures and, even more dramatically, in the cultures treated with high Ca plus PTH, with consistent up-regulation of the expression levels of osteoblast proliferation and differentiation-related genes and proteins. These results indicate that dietary Ca and PTH play synergistic roles in promoting osteoblastic bone formation by stimulating osteoblast proliferation and differentiation.
Department of Orthopaedics,The First Affiliated Hospital, Nanjing Medical University,Nanjing, Jiangsu,People's Republic of China.
Yuxu
Y
Feng
Department of Orthopaedics,The First Affiliated Hospital, Nanjing Medical University,Nanjing, Jiangsu,People's Republic of China.
Min
M
Zhou
Department of Orthopaedics,The First Affiliated Hospital, Nanjing Medical University,Nanjing, Jiangsu,People's Republic of China.
Qunhu
Q
Zhang
Department of Orthopaedics,The First Affiliated Hospital, Nanjing Medical University,Nanjing, Jiangsu,People's Republic of China.
Huan
H
Liu
Department of Orthopaedics,The First Affiliated Hospital, Nanjing Medical University,Nanjing, Jiangsu,People's Republic of China.
Yong
Y
Xu
Department of Geriatric Endocrinology,Jinling Hospital, Nanjing University School of Medicine,Nanjing,People's Republic of China.
Lei
L
Shu
Department of Emergency,The Affiliated Jiangning Hospital of Nanjing Medical University,Nanjing, Jiangsu,People's Republic of China.
Jue
J
Zhang
Center for Bone and Stem Cell Research, Nanjing Medical University,Nanjing, Jiangsu,People's Republic of China.
Dengshun
D
Miao
Department of Orthopaedics,The First Affiliated Hospital, Nanjing Medical University,Nanjing, Jiangsu,People's Republic of China.
Yongxin
Y
Ren
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002136:Calcium, Dietary / Q000378:metabolism / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D018565:Food-Drug Interactions; D008297:Male; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D018016:Receptors, Parathyroid Hormone / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D050071:Bone Density Conservation Agents; D015220:Calcium Channels; D002136:Calcium, Dietary; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D044169:Receptors, Calcium-Sensing; D018016:Receptors, Parathyroid Hormone; D050916:TRPV Cation Channels; C446923:Trpv6 protein, mouse
Bone formation