Int J Oral Biol.  2019 Sep;44(3):89-95. 10.11620/IJOB.2019.44.3.89.

Piperlongumine suppressed osteoclastogenesis in RAW264.7 macrophages

  • 1Department of Oral and Maxillofacial Surgery, Pusan National University Dental Hospital, Yangsan 50612, Republic of Korea.
  • 2Department of Oral Anatomy, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea.,
  • 3BK21 PLUS Project, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea.


Piperlongumine (PL) is a natural product found in long pepper (Piper longum). The pharmacological effects of PL are well known, and it has been used for pain, hepatoprotection, and asthma in Oriental medicine. No studies have examined the effects of PL on bone tissue or bone-related diseases, including osteoporosis. The current study investigated for the first time the inhibitory effects of PL on osteoclast differentiation, bone resorption, and osteoclastogenesis-related factors in RAW264.7 macrophages stimulated by the receptor activator for nuclear factor-κB ligand (RANKL). Cytotoxicity was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and osteoclast differentiation and bone resorption were confirmed by tartrate-resistant acid phosphatase (TRAP) staining and pit formation analysis. Osteoclast differentiation factors were confirmed by western blotting. PL exhibited toxicity in RAW264.7 macrophages, inhibiting osteoclast formation and bone resorption, in addition to inhibiting the expression of osteoclastogenesis-related factors, such as tumor necrosis factor receptor-associated factor 6 (TRAF6), c-Fos, and NFATc1, in RANKL-stimulated RAW264.7 macrophages. These findings suggest that PL is suitable for the treatment of osteoporosis, and it serves as a potential therapeutic agent for various bone diseases.


Piper longum; Osteoclastogenesis; Osteoporosis; Macrophagy
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