Osteopontin deficiency suppresses high phosphate load-induced bone loss via specific modulation of osteoclasts.
Phosphate (Pi) plays a critical role in the maintenance of mineralized tissues and signaling in the intracellular environment. Although extracellular phosphate concentration is maintained at fixed levels, physiological machineries involved in phosphate homeostasis in bone, which is the largest phosphate storage site, have not yet been fully elucidated. Here we examined the role of osteopontin (OPN) in a high-Pi diet load-induced bone loss. A high-Pi diet significantly reduced bone mineral density as well as bone mass in wild type. In contrast, OPN deficiency totally prevented reduction in bone mineral density and bone mass. Analyses of bone turnover-related components revealed that bone formation parameters (bone formation rate and mineral apposition rate) were enhanced by high-Pi diet load similarly in wild-type and OPN-deficient mice. In sharp contrast, bone resorption parameters (osteoclast number and osteoclast surface) were enhanced by high-Pi diet load in wild type but not at all in OPN-deficient mice. Bone marrow cell cultures revealed no major effects of OPN deficiency on high-Pi diet modulation of mineralized nodule formation in culture. On the other hand, tartrate-resistant acid phosphatase-positive multinucleated cell development in cultures were enhanced by high-Pi diet load in wild-type cells, but such effects of high Pi-diet were totally abolished in the absence of OPN. These data indicated that OPN is needed for osteoclastic activity to resorb bone on high phosphate loading.
Koyama
Yuki
Y
Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
Rittling
Susan R
SR
Tsuji
Kunikazu
K
Hino
Kazunori
K
Salincarnboriboon
Ruchanee
R
Yano
Tetsu
T
Taketani
Yuji
Y
Nifuji
Akira
A
Denhardt
David T
DT
Noda
Masaki
M
D000818:Animals; D015519:Bone Density; D001862:Bone Resorption / Q000209:etiology*; D002478:Cells, Cultured; D005260:Female; D051379:Mice; D010010:Osteoclasts / Q000502:physiology*; D010012:Osteogenesis; D053495:Osteopontin; D010710:Phosphates / Q000008:administration & dosage*; D012795:Sialoglycoproteins / Q000502:physiology*
D010710:Phosphates; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin