Jin, Sun-Mi
(Department of Oral and Maxillofacial Surgery, Pusan National University Dental Hospital)
,
Kang, Hae-Mi
(Department of Oral Anatomy, School of Dentistry, Pusan National University)
,
Park, Dan-Bi
(Department of Oral Anatomy, School of Dentistry, Pusan National University)
,
Yu, Su-Bin
(Department of Oral Anatomy, School of Dentistry, Pusan National University)
,
Kim, In-Ryoung
(Department of Oral Anatomy, School of Dentistry, Pusan National University)
,
Park, Bong-Soo
(Department of Oral Anatomy, School of Dentistry, Pusan National University)
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, includ...
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-${\kappa}B$ 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.
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-${\kappa}B$ 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.
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제안 방법
The proton pump is activated in the ruffled membrane of mature osteoclasts in contact with the substrate to create an acidic microenvironment to melt the bone matrix and form a “pit-like” structure [23]. In this study, treatment with RANKL alone induced macrophage fusion/differentiation into multi-nucleated osteoclasts in RAW264.7 macrophages, and combination treatment with RANKL and PL inhibited TRAP-positive osteoclasts and bone resorption pits in a dose-dependent manner.
대상 데이터
A murine macrophage cell line, RAW264.7, was obtained from the Korean Cell Line Bank (Seoul, Korea). The cells were maintained in HyCloneTM Dulbecco Modified Eagle’s Medium(DMEM; HyClone, Logan, UT, USA) with 10% heat-inactivated fetal bovine serum (FBS; HyClone) at 37℃ in a 5% CO2 incubator.
데이터처리
A one-way ANOVA, followed by Dunnett’s multiple comparison test was used to analyze cell viability, TRAP positivity, pit formation, and Western blot data.
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