Puerarin Prevents LPS-Induced Osteoclast Formation and Bone Loss via Inhibition of Akt Activation
| Autor: | Yun-feng Gao, Qing-feng Yu, Zhi-fen Zhang, Yong-hong Sun, Yun Zhang, Ming Yan, Hai-dong Zhang, Pei-fan Yang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pharmacology Osteolysis Pharmaceutical Science Interleukin General Medicine medicine.disease 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology medicine.anatomical_structure chemistry Puerarin Osteoclast Cathepsin K medicine Cancer research Tumor necrosis factor alpha Prostaglandin E2 Protein kinase B medicine.drug |
| Zdroj: | Biological & Pharmaceutical Bulletin. 39:2028-2035 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.b16-00522 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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