Osteopontin deficiency induces parathyroid hormone enhancement of cortical bone formation.
Intermittent PTH treatment increases cancellous bone mass in osteoporosis patients; however, it reveals diverse effects on cortical bone mass. Underlying molecular mechanisms for anabolic PTH actions are largely unknown. Because PTH regulates expression of osteopontin (OPN) in osteoblasts, OPN could be one of the targets of PTH in bone. Therefore, we examined the role of OPN in the PTH actions in bone. Intermittent PTH treatment neither altered whole long-bone bone mineral density nor changed cortical bone mass in wild-type 129 mice, although it enhanced cancellous bone volume as reported previously. In contrast, OPN deficiency induced PTH enhancement of whole-bone bone mineral density as well as cortical bone mass. Strikingly, although PTH suppressed periosteal bone formation rate (BFR) and mineral apposition rate (MAR) in cortical bone in wild type, OPN deficiency induced PTH activation of periosteal BFR and MAR. In cancellous bone, OPN deficiency further enhanced PTH increase in BFR and MAR. Analysis on the cellular bases for these phenomena indicated that OPN deficiency augmented PTH enhancement in the increase in mineralized nodule formation in vitro. OPN deficiency did not alter the levels of PTH enhancement of the excretion of deoxypyridinoline in urine, the osteoclast number in vivo, and tartrate-resistant acid phosphatase-positive cell development in vitro. These observations indicated that OPN deficiency specifically induces PTH activation of periosteal bone formation in the cortical bone envelope.
Kitahara
Keiichiro
K
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
Ishijima
Muneaki
M
Rittling
Susan R
SR
Tsuji
Kunikazu
K
Kurosawa
Hisashi
H
Nifuji
Akira
A
Denhardt
David T
DT
Noda
Masaki
M
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D002478:Cells, Cultured; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D053495:Osteopontin; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010521:Periosteum / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000172:deficiency*
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin