title: Puerarin Prevents LPS-Induced Osteoclast Formation and Bone Loss via Inhibition of Akt Activation.
abstract: Osteolysis induced by chronic Gram-negative bacterial infection underlies many bone diseases such as osteomyelitis, septic arthritis, and periodontitis. Drugs that inhibit lipopolysaccharide (LPS)-induced osteolysis are critically needed for the prevention of bone destruction in infective bone diseases. In this study, we assessed the effect of puerarin, a natural isoflavone isolated from Pueraria lobata OHWI root, on LPS-induced osteoclastogenesis and bone loss. Our in vitro study showed that puerarin significantly inhibited LPS-induced osteoclast differentiation from osteoclast precursor RAW264.7 cells. The inhibition occurred through suppressing the production of osteoclast activating factor tumor necrosis factor (TNF)-α, interleukin (IL)-1β and prostaglandin E2(PGE2), which led to down-regulating mRNA expression of osteoclastogenic genes including tartrate-resistant acid phosphatase (TRAP), cathepsin K and matrix metalloprotein 9 (MMP-9). Furthermore, LPS triggered activation of Akt in osteoclast precursor RAW264.7 cells, which was inhibited by puerarin treatment. In vivo, puerarin attenuated LPS-induced bone loss in a murine calvarial osteolysis model. Collectively, puerarin prevents LPS-induced osteoclast formation, function and bone loss, where the inhibition of Akt activation plays an important role. These findings provide evidences that puerarin might be beneficial as a promising candidate drug for the prevention and treatment of bacteria-induced bone destruction disease, and give new insights for understanding its possible mechanism.
authors.affiliation: College of Medicine, Shaoxing University.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Qing-Feng
authors.initials: QF
authors.lastname: Yu
authors.forename: Pei-Fan
authors.initials: PF
authors.lastname: Yang
authors.forename: Hai-Dong
authors.initials: HD
authors.lastname: Zhang
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Sun
authors.forename: Zhi-Fen
authors.initials: ZF
authors.lastname: Zhang
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Gao
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000067996:RAW 264.7 Cells; D012886:Skull / Q000187:drug effects / Q000473:pathology
chemical_list: D016207:Cytokines; D007529:Isoflavones; D008070:Lipopolysaccharides; D051057:Proto-Oncogene Proteins c-akt; C033607:puerarin