Puerarin Prevents LPS-Induced Osteoclast Formation and Bone Loss via Inhibition of Akt Activation.
Biol Pharm Bull
; 39(12): 2028-2035, 2016.
Article
en En
| MEDLINE
| ID: mdl-27904045
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)-1ß 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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Osteoclastos
/
Resorción Ósea
/
Proteínas Proto-Oncogénicas c-akt
/
Isoflavonas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biol Pharm Bull
Asunto de la revista:
BIOQUIMICA
/
FARMACOLOGIA
Año:
2016
Tipo del documento:
Article