期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 78, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2019.106014
关键词
Flufenamic acid; Osteoclast differentiation; Osteoporosis; MAPK; RNA-Seq
资金
- National Natural Science Foundation of China [81472119, 81672196]
- Shanghai Rising Stars of Medical Talent Youth Development Program (Youth Medical Talents - Specialist Program)
Postmenopausal osteoporosis is one of the most common types of osteoporosis resulting from estrogen deficiency in elderly women. Nonsteroidal anti-inflammatory drugs (NSAIDs) are important drugs for pain relief in patients with osteoporosis. In this study, we report for the first time that flufenamic acid, a clinically approved and widely used NSAID, not only has analgesic properties but also shows a significant effect in terms of preventing postmenopausal osteoporosis. Quantitative RT-PCR analysis showed that treatment with flufenamic acid significantly downregulated the genes associated with osteoclast differentiation. Meanwhile, RNA-sequencing and western blot analyses suggested that flufenamic acid could inhibit the bone resorption by suppressing the phosphorylation of MAPK pathways. Moreover, an ovariectomy (OVX)-induced bone-loss mouse model indicated that flufenamic acid might be a potent drug for preventing osteoporotic fractures, as verified by micro-CT scanning and histological analysis. Therefore, this study proposes an attractive and potent drug with analgesic properties for the prevention of postmenopausal osteoporosis.
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