ABSTRACT
UNLABELLED: The purpose of this study is to investigate the dose-dependent effects of SWH on bone properties and the mechanism involved in mediating the osteoprotective actions of SWH. The results indicated that SWH could improve bone properties by inhibiting the process of bone resorption and stimulating the process of bone formation. INTRODUCTION: Our previous study showed that Sambucus williamsii HANCE (SWH) improved trabecular bone mass and cortical bone strength in ovariectomized (OVX) rats. The purpose of this study is to investigate the dose-dependent effects of SWH on bone properties and the mechanism involved in mediating the osteoprotective actions of SWH. METHODS: Three-month-old C57BL/6J mice were fed a phytoestrogen-free diet and subjected to either ovariectomy or sham operation. OVX mice were treated with genistein (50 mg/kg), or a low (200 mg/kg), medium (500 mg/kg), or high (1,000 mg/kg) dose of SWH extract. RESULTS: SWH could dose-dependently decrease urinary Ca excretion and increase serum Ca level in OVX mice. It could increase tibial bone mineral density and exert beneficial effects on the microarchitecture of trabecular bone in the OVX mice. SWH suppressed the ovariectomy-induced expression of Cbfa1 mRNA and cathepsin K mRNA and enhanced the ratio of OPG/RANKL mRNA expression in the tibia. In vitro study showed that SWH dramatically reduced the number of TRAP-positive cells in RANKL-induced RAW 264.7 cells. CONCLUSIONS: The present study indicated that SWH could improve bone properties by inhibiting the process of bone resorption and stimulating the process of bone formation.
Subject(s)
Bone Resorption/metabolism , Osteoporosis/drug therapy , Plant Extracts/pharmacology , Sambucus , Acid Phosphatase/metabolism , Animals , Bone Density/drug effects , Calcium/blood , Calcium/metabolism , Case-Control Studies , Cathepsin K/metabolism , Cell Line , Core Binding Factor Alpha 1 Subunit/drug effects , Core Binding Factor Alpha 1 Subunit/metabolism , Eye Proteins/drug effects , Eye Proteins/metabolism , Female , Hindlimb , Homeodomain Proteins/drug effects , Homeodomain Proteins/metabolism , Isoenzymes/metabolism , Mice , Mice, Inbred C57BL , Osteoprotegerin/drug effects , Osteoprotegerin/metabolism , Ovariectomy , RANK Ligand/metabolism , Tartrate-Resistant Acid Phosphatase , Tibia , Transcription Factors/drug effects , Transcription Factors/metabolism , Treatment OutcomeABSTRACT
The HSP70 family of heat shock proteins, which are involved in development and cellular differentiation, is elevated in various tumor cell lines. To examine the role of these proteins in neoplastic cell differentiation, four members of the HSP70 multiple gene family (i.e., HSP70, HSC70, GRP78, and mtHSP70) were examined during the induced differentiation of HL-60 promyelocytic leukemia cells. Western analyses showed that continuous exposure for 48 h of HL-60 cells to the differentiation-inducing agents, all-trans retinoic acid, 1,25-dihydroxyvitamin D3, or N-methylformamide, resulted in decreases in mitochondrial HSP70 (mtHSP70), with little change in the levels of HSP70, HSC70, and GRP78. To gain information on the role of mtHSP70 in the differentiation process, HL-60 cells were transfected with either murine mthsp70 cDNA or vector alone. Slightly greater than twofold increases in mtHSP70 protein levels occurred in cells transfected with the mthsp70 cDNA. In vector-transfected HL-60 cells, myeloid differentiation, measured as an increase in CD31 expression and nitroblue tetrazolium positivity, was observed following 3-6 days of treatment with each of the three inducing agents. In contrast, cell differentiation induced by each agent was markedly attenuated in mthsp70-transfected HL-60 cells. These findings suggest that a decrease in mtHSP70 is important for the induced differentiation of HL-60 cells.
