The effects of luteolin on osteoclast differentiation, function in vitro and ovariectomy-induced bone loss.
Flavonoids, a group of polyphenolic compounds abundant in plants, are known to prevent bone loss in ovariectomized (OVX) animal models. Inhibition of osteoclast differentiation and bone resorption is considered as an effective therapeutic approach in the treatment of postmenopausal bone loss. Luteolin, a plant flavonoid, has potent anti-inflammatory properties both in vivo and vitro. In this study, we found that luteolin markedly decreased the differentiation of both bone marrow mononuclear cells and Raw264.7 cells into osteoclasts. Luteolin also inhibited the bone resorptive activity of differentiated osteoclasts. We further investigated the effects of luteolin on ovariectomy-induced bone loss using micro-computed tomography, biomechanical tests and serum markers assay for bone remodeling. Oral administration of luteolin (5 and 20 mg/kg per day) to OVX mice caused significant increase in bone mineral density and bone mineral content of trabecular and cortical bones in the femur as compared to those of OVX controls, and prevented decreases of bone strength indexes induced by OVX surgery. Serum biochemical markers assays revealed that luteolin prevents OVX-induced increases in bone turnover. These data strongly suggest that luteolin has the potential for prevention of bone loss in postmenopausal osteoporosis by reducing both osteoclast differentiation and function.
Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Jung-gu, Daegu 700-412, Republic of Korea. archion@knu.ac.kr
Tae-Ho
TH
Kim
Ji Won
JW
Jung
Byung Geun
BG
Ha
Jung Min
JM
Hong
Eui Kyun
EK
Park
Hyun-Ju
HJ
Kim
Shin-Yoon
SY
Kim
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D001862:Bone Resorption / Q000517:prevention & control*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D047311:Luteolin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism / Q000517:prevention & control*; D010052:Ovariectomy; D011859:Radiography; D011897:Random Allocation
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D047311:Luteolin