title: Effect of Buthus martensi Karsch on aromatase activity and cytokine-inducted NOS and NO production in osteoblasts and leukaemic cell line FLG 29.1.
abstract: Among the different scorpion species, Buthus martensi Karsch, a widely distributed scorpion species in Asia especially in Korea, has received a lot of attention. Indeed, over the past decade, more than 70 different peptides, toxins, or homologues have been isolated. It may prove a valuable resource for identifying potential anti-inflammatory and analgesic drugs. The recent observation has suggested that the aromatase is a possible local modulator of bone remodeling in osteoarthritis and osteoporosis. In the present study, therefore, the effect of Buthus martensi Karsch (BMK) extract, traditional immunosuppressive Korean aqua-acupuncture water, on the bone function of human osteoblastic cells was studied. To provide insights into the effect of BMK on aromatase activity in bone-derived cells, we examined the human leukaemic cell line FLG 29.1, which is induced to differentiate toward the osteoclastic phenotype by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and transforming growth factor (TGF)-beta1, and the primary first-passage osteoblastic cells (hOB). Gene expression of the aromatase was not affected by Buthus martensi Karsch in FLG 29.1 and hOB cells. However, enzyme activity was stimulated in a time-dependent fashion by 10.0 microg/ml BMK and by either 1-50 nM TPA or 0.01-0.5 ng/ml TGF-beta1, with maximal responses after 2-3 hr exposure. On the other hand, BMK strongly inhibited interleukin-1beta (IL-1beta)- and tumor necrosis factor (TNF)alpha-induced Nitricoxide (NO) synthase expression with little effect on constitutive NO synthase expression. BMK extracts (10 microg/ml) inhibited cytokine-induced iNOS and nNOS expression. BMK (10 microg/ml) did not affect the ecNOS expression, indicating the extracts are not working on the constitutive NOS expression. BMK strongly inhibited the cytokine-induced NO production (p < 0.01). BMK also showed significant inhibition on NO production in both induced by TNF-alpha+IL-1beta. NO donors, sodium nitroprusside, and NONOate dose-dependently elevated alkaline phosphatase activity. These results suggest that NO directly facilitates osteoblastic differentiation. This result also suggests that BMK is effective for bone resorptive action in bone cells.
authors.affiliation: Molecular and Cellular Glycobiology Unit, Department of Biological Science, SungKyunKwan University, Suwon City, Kyunggi, Korea.
authors.forename: Un-Ho
authors.initials: UH
authors.lastname: Jin
authors.forename: Kap-Sung
authors.initials: KS
authors.lastname: Kim
authors.forename: Su-Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Kang-Hyun
authors.initials: KH
authors.lastname: Chung
authors.forename: Dong-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001141:Aromatase / Q000096:biosynthesis*; D015415:Biomarkers / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D045424:Complex Mixtures / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D000091344:Filaggrin Proteins; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism; D012605:Scorpions / Q000737:chemistry
chemical_list: D015415:Biomarkers; D045424:Complex Mixtures; D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D001141:Aromatase