Inhibition of osteoclast differentiation and bone resorption by tanshinone IIA isolated from Salvia miltiorrhiza Bunge.
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.
Kim
Hong-Hee
HH
Research Center for Proteineous Materials, Gwangju 501-759, South Korea.
Kim
Jung Ha
JH
Kwak
Han Bok
HB
Huang
Hao
H
Han
Song-Hee
SH
Ha
Hyunil
H
Lee
Soo Woong
SW
Woo
Eun-Ran
ER
Lee
Zang Hee
ZH
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
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