title: Inhibition of osteoclast differentiation and bone resorption by tanshinone IIA isolated from Salvia miltiorrhiza Bunge.
abstract: Osteoclasts, multinuclear cells specialized for bone resorption, differentiate from the monocyte/macrophage lineage of hematopoietic cells. Intervention in osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone diseases involving osteoclasts. In this study, we found that tanshinone IIA, originating from Salvia miltiorrhiza Bunge, inhibited the differentiation of osteoclasts. Addition of tanshinone IIA to the osteoclast precursor culture caused a significant decrease in the level of calcitonin receptor, c-Src, and integrin beta3 mRNA, which are normally upregulated during the osteoclast differentiation dependent on RANKL (receptor activator of nuclear factor kappa B ligand). RANKL activated the ERK, Akt, and NF-kappaB signal transduction pathways in osteoclast precursor cells, and tanshinone IIA suppressed this activation. Tanshinone IIA also inhibited the bone resorptive activity of differentiated osteoclasts, which was accompanied with the disruption of the actin ring. Thus, tanshinone IIA has the potential to ameliorate bone-resorption diseases in vivo by reducing both the number and activity of osteoclasts.
authors.affiliation: Research Center for Proteineous Materials, Gwangju 501-759, South Korea.
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
authors.forename: Jung Ha
authors.initials: JH
authors.lastname: Kim
authors.forename: Han Bok
authors.initials: HB
authors.lastname: Kwak
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.forename: Song-Hee
authors.initials: SH
authors.lastname: Han
authors.forename: Hyunil
authors.initials: H
authors.lastname: Ha
authors.forename: Soo Woong
authors.initials: SW
authors.lastname: Lee
authors.forename: Eun-Ran
authors.initials: ER
authors.lastname: Woo
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Lee
mesh_terms: D045784:Abietanes; D000199:Actins / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells; D001862:Bone Resorption / Q000188:drug therapy; D002454:Cell Differentiation / Q000187:drug effects*; D002459:Cell Fusion; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D053244:Osteoprotegerin; D010616:Phenanthrenes / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D045784:Abietanes; D000199:Actins; D006023:Glycoproteins; D016328:NF-kappa B; D053244:Osteoprotegerin; D010616:Phenanthrenes; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506031:Tnfrsf11b protein, mouse; C021751:tanshinone; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases