ABSTRACT
BACKGROUND: Rehmannia glutinosa Libosch extracts (RGX) were investigated to determine if they play roles in bone metabolism. METHODS: The effects on osteoblasts were determined by measuring (1) cell proliferation, (2) alkaline phosphatase (ALP) activity, (3) mRNA expression of bone-related proteins, (4) transcriptional activity of Runx2, and (5) osteoprotegerin (OPG) secretion. The effects on the osteoclasts were investigated by measuring (1) tartrate-resistant acid phosphatase-positive [TRAP(+)] multinucleated cell (MNC) formation and (2) resorption areas after culturing osteoclast precursors. Bone mineral density (BMD) measurements and histological observations on rats were also carried out. RESULTS: RGX treatment showed a significant increase in both the proliferation and ALP activity of osteoblasts. RGX increased the expression of the bone-related genes. OPG secretion was markedly increased after RGX treatment. In addition, RGX treatment decreased the number of TRAP(+) MNCs and the resorption areas. In vivo studies using ovariectomy-induced osteoporotic rats revealed that RGX alleviated the decrease in the trabecular BMD, and increased the cortical bone thickness and trabeculation of the bone marrow spaces. CONCLUSIONS: RGX stimulates the proliferation and activities of osteoblasts, while inhibiting the generation and resorptive activities of osteoclasts. It also shows preventive effects on osteoporotic bone loss induced by an ovariectomy. Although the active substances have not yet been identified, it is believed that the RGX seems to contain active components that have a potential to enhance the bone metabolism in osteoporosis.
Subject(s)
Bone and Bones/metabolism , Neoplasm Proteins , Rehmannia/chemistry , Alkaline Phosphatase/metabolism , Animals , Bacterial Proteins/metabolism , Bone Density/drug effects , Bone Marrow Cells/metabolism , Bone Resorption/metabolism , Bone and Bones/drug effects , Bone and Bones/enzymology , Cell Division/drug effects , Cell Line , Collagen Type I/metabolism , Core Binding Factor Alpha 1 Subunit , Female , Humans , Mice , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteopontin , Osteoporosis/drug therapy , Ovariectomy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , RNA, Messenger/biosynthesis , RNA-Binding Proteins/metabolism , Rats , Rats, Sprague-Dawley , Sialoglycoproteins/metabolism , Transcription Factors/biosynthesis , Transcription Factors/genetics , Transcription Factors/metabolism , Transcription, GeneticABSTRACT
Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor superfamily, is known to inhibit osteoclastogenesis by acting as a soluble decoy receptor for the receptor activator of NF-kappaB ligand (RANKL). We report the presence of OPG on the membrane of osteoclasts and the possibility of the direct action of OPG on them. Highly pure osteoclast precursors were isolated from mouse long bones and induced to differentiate into mature osteoclasts by M-CSF and soluble RANKL (sRANKL). The presence of OPG on the membrane of these cells was confirmed by western blotting and immunostaining. Furthermore, sRANKL was found to be bound to the OPG on the osteoclast precursors. These results suggest that OPG might have a new role during the differentiation of osteoclasts beyond its role as a soluble decoy receptor. The mechanism of the existence of OPG on osteoclast precursors remains to be found.
