Hayashibara Tetsuyuki, Hiraga Toru, Sugita Atsushi, Wang Liyang, Hata Kenji, Ooshima Takashi, Yoneda Toshiyuki
Department of Biochemistry, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
J Bone Miner Res. 2007 Nov;22(11):1743-51. doi: 10.1359/jbmr.070709.
Mice fed with a low Pi diet exhibited decreased osteoclast number. Hyp mice also showed decreased osteoclasts, and high Pi reversed it. Low Pi reduced osteoclast formation and bone resorption in vitro. Hypophosphatemia may suppress osteoclast differentiation/function, leading to skeletal abnormalities.
Skeletal abnormalities seen in hypophosphatemic disorders indicate a critical role of phosphate (Pi) in skeletogenesis. However, the role of osteoclasts in the pathogenesis of the disturbed skeletogenesis is unclear.
Mice fed with a low-Pi diet and Hyp mice that are characterized by hypophosphatemia and impaired osteogenesis were studied. Effects of Pi on osteoclast formation and bone resorption were also examined in vitro.
Histomorphometric examination showed that mice on a low-Pi diet exhibited decreased osteoclast number. Furthermore, osteoclast number in Hyp mice was also decreased compared with wildtype (WT) mice. Of note, feeding of Hyp mice with high-Pi diet significantly reversed hypophosphatemia, improved disturbed osteogenesis, and increased osteoclast number. Osteoclast-like cell (OLC) formation and bone resorption in Hyp bone marrow cells was not different from WT bone marrow cells. On the other hand, OLC formation and bone resorption were decreased in conjunction with reduced mRNA expression of RANKL in WT bone marrow cells cultured in the medium containing low Pi (0.5 mM). Recombinant human matrix extracellular phosphoglycoprotein (MEPE), a candidate for phosphatonin, also decreased osteoclast formation, whereas fibroblast growth factor 23 (FGF23), another phosphatonin candidate, showed no effects.
Our results suggest that Pi controls the differentiation and function of osteoclasts. These actions of Pi on osteoclasts may be associated with the pathogenesis of the skeletal abnormalities in hypophosphatemic disorders.
喂食低磷饮食的小鼠破骨细胞数量减少。Hyp小鼠的破骨细胞也减少，高磷可使其逆转。低磷在体外可减少破骨细胞形成和骨吸收。低磷血症可能抑制破骨细胞分化/功能，导致骨骼异常。
低磷血症性疾病中出现的骨骼异常表明磷酸盐（Pi）在骨骼发育中起关键作用。然而，破骨细胞在骨骼发育紊乱发病机制中的作用尚不清楚。
研究了喂食低磷饮食的小鼠以及以低磷血症和成骨受损为特征的Hyp小鼠。还在体外检测了磷对破骨细胞形成和骨吸收的影响。
组织形态计量学检查显示，喂食低磷饮食的小鼠破骨细胞数量减少。此外，与野生型（WT）小鼠相比，Hyp小鼠的破骨细胞数量也减少。值得注意的是，给Hyp小鼠喂食高磷饮食可显著逆转低磷血症，改善成骨紊乱，并增加破骨细胞数量。Hyp骨髓细胞中破骨细胞样细胞（OLC）的形成和骨吸收与WT骨髓细胞无差异。另一方面，在含低磷（0.5 mM）培养基中培养的WT骨髓细胞中，OLC形成和骨吸收减少，同时RANKL的mRNA表达降低。磷调节素候选物重组人基质细胞外磷酸糖蛋白（MEPE）也可减少破骨细胞形成，而另一种磷调节素候选物成纤维细胞生长因子23（FGF23）则无作用。
我们的结果表明磷控制破骨细胞的分化和功能。磷对破骨细胞的这些作用可能与低磷血症性疾病中骨骼异常的发病机制有关。
