The effect of the level of casein phosphopeptide (CPP) on mineral (Ca and P) bioavailabilties and bone biomarker of aged ovariectomized (OVX) Sprague-Dawley rats were studied as a model for postmenopausal bone loss. Forty five Spargue dawley rats, 220-230g of body weight were fed a control diet (AIN 93M) or containing different level of CPP diet for 7 weeks: 0% (sham control; SC, OVX control; OC), 1% (OVX low CPP diet; OL), 2% (OVX medium CPP diet; OM), 3% (OVX high CPP diet; OH) Ca absorption was unaffected by increasing CPP content from 0 to 3%. Urinary Ca excretion was increased by OVX, and decreased by CPP significantly (p<0.05) with no evident dose-relationship. The urinary P excretion was increased by CPP intake in OVX rats. The fecal excretion of P given CPP decreased in OVX with dose dependent manner. Ca and P contents of femur significantly increased by adding 2 or 3% of CPP when compared with OC group and OL group (p<0.05). There were no significant differences in serum alkaline phosphatase activity and c-terminal telopeptide excretion in experimental groups. Although ovariectomy induced the increase in urinary c-terminal telopeptide excretion, 2 or 3% of CPP in the diet decreased urinary c-terminal telopetide excretion significantly. These finding suggest the usefulness of CPP in the prevention of postmenopausal bone loss by decreasing urinary Ca excretion and bone resorption. Over 2 percent of CPP in the diet was effective to prevent postmenopausal bone loss.
Absorption ; Alkaline Phosphatase ; Animals ; Body Weight ; Bone Resorption ; Calcium ; Caseins ; Diet ; Female ; Femur ; Humans ; Metabolism* ; Osteoporosis, Postmenopausal ; Ovariectomy ; Phosphorus ; Rats* ; Rats, Sprague-Dawley

Bone is a dynamic tissue that is regulated by the activity of bone-resorbing osteoclasts and bone-forming osteoblasts. Excessive osteoclast formation causes diseases such as osteoporosis and rheumatoid arthritis. Natural substances may be useful as therapeutic drugs to prevent many diseases in humans because they avoid the many side effects of treatment with chemical compounds. Here we show that tanshinone IIA isolated from Salvia miltiorrhiza Bunge inhibits the receptor activator of NF-kappaB ligand (RANKL)-mediated osteoclast differentiation of osteoclast precursors. Tanshinone IIA suppressed the expression levels of c-Fos and NFATc1 induced by RANKL. However, retrovirus-mediated overexpression of c-Fos induced the expression of NFATc1 despite the presence of tanshinone IIA and reversed the inhibitory effect of tanshinone IIA on osteoclast differentiation. Also, the introduction of osteoclast precursors with the NFATc1 retrovirus led to osteoclast differentiation in the presence of tanshinone IIA. Our results suggest that tanshinone IIA may have a role as a therapeutic drug in the treatment of bone disease such as osteoporosis.
Reverse Transcriptase Polymerase Chain Reaction ; Receptor Activator of Nuclear Factor-kappa B ; RANK Ligand ; Proto-Oncogene Proteins c-fos/genetics/*metabolism ; Phenanthrenes/*pharmacology ; Osteoclasts/cytology/*drug effects/metabolism ; NFATC Transcription Factors/genetics/*metabolism ; Mice, Inbred ICR ; Mice ; Membrane Glycoproteins/genetics/metabolism/pharmacology ; Male ; Macrophage Colony-Stimulating Factor/pharmacology ; Immunoblotting ; Gene Expression/drug effects/genetics ; Down-Regulation/drug effects ; Cells, Cultured ; Cell Differentiation/*drug effects ; Carrier Proteins/genetics/metabolism/pharmacology ; Bone Marrow Cells/cytology/drug effects/metabolism ; Animals