Sophorae Flos extract inhibits RANKL-induced osteoclast differentiation by suppressing the NF-κB/NFATc1 pathway in mouse bone marrow cells.
BACKGROUND
Sophorae Flos (SF) is a composite of flowers and buds of Styphnolobium japonicum (L.) Schott and has been used in traditional Korean and Chinese medicine for the treatment of hemostasis and inflammation. Previous studies reported that SF possesses anti-obesity properties, as well as anti-allergic, anti-proliferative, and anti-inflammatory activities. However, the effect of SF in bone resorption has not been studies. In this study, we examined the potential of SF extract (SFE) to inhibit receptor activator of NF-κB ligand (RANKL) -induced osteoclast differentiation in cultured mouse-derived bone marrow macrophages (BMMs).


METHODS
BMMs, that act as osteoclast precursors, were cultured with M-CSF (50 ng/ml) and RANKL (100 ng/ml) for 4 days to generate osteoclasts. Osteoclast differentiation was measured by tartrate-resistant acidic phosphatase (TRAP) staining and the TRAP solution assay. Osteoclast differentiation marker genes were analyzed by the quantitative real-time polymerase chain reaction analysis. RANKLs signaling pathways were confirmed through western blotting.


RESULTS
SFE significantly decreased osteoclast differentiation in a dose-dependent manner. SFE inhibited RANKL-induced osteoclastogenesis by suppressing NF-κB activation. By contrast, SFE did not affect phospholipase C gamma 2 or subsequent cAMP response element binding activation. SFE inhibited the RANKL-induced expression of nuclear factor of activated T cells c1 (NFATc1).


CONCLUSIONS
SFE attenuated the RANKL-mediated induction of NF-κB through inhibition of IκBα phosphorylation, which contributed to inhibiting of RANKL-induced osteoclast differentiation through downregulation of NFATc1.
Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan, 570-749, Republic of Korea.
Jeong-Mi
JM
Kim
Department of Rehabilitation Medicine of Korean Medicine, Wonkwang University School of Korean Medicine, Iksan City, Jeonbuk, 570-749, Republic of Korea.
Jung-Han
JH
Lee
Department of Herbology, Wonkwang University School of Korean Medicine, Iksan, 570-749, Republic of Korea.
Guem-San
GS
Lee
Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan, 570-749, Republic of Korea.
Eun-Mi
EM
Noh
Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan, 570-749, Republic of Korea.
Hyun-Kyung
HK
Song
Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan, 570-749, Republic of Korea.|Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan, 570-749, Republic of Korea.
Dong Ryun
DR
Gu
Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan, 570-749, Republic of Korea.|Department of Korean Physiology, Wonkwang University School of Korean Medicine, Iksan City, Jeonbuk, 570-749, Republic of Korea.
Seong-Cheol
SC
Kim
Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan, 570-749, Republic of Korea.|Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan, 570-749, Republic of Korea.|Integrated Omics institute, Wonkwang University, Iksan, 570-749, Republic of Korea.
Seoung Hoon
SH
Lee
Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan, 570-749, Republic of Korea. desson@wku.ac.kr.|Department of Korean Physiology, Wonkwang University School of Korean Medicine, Iksan City, Jeonbuk, 570-749, Republic of Korea. desson@wku.ac.kr.
Kang-Beom
KB
Kwon
Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan, 570-749, Republic of Korea. mindyr@wku.ac.kr.|Department of Oral Biochemistry, and Institute of Biomaterial-Implant, College of Dentistry, Wonkwang University, Iksan, 570-749, Republic of Korea. mindyr@wku.ac.kr.|Integrated Omics institute, Wonkwang University, Iksan, 570-749, Republic of Korea. mindyr@wku.ac.kr.
Young-Rae
http://orcid.org/0000-0002-2119-2609
YR
Lee
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D035264:Flowers / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D029909:Sophora / Q000737:chemistry*
D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D010936:Plant Extracts; D053245:RANK Ligand
NF-κB; NFATc1; Osteoclast; PLCγ2; Sophorae Flos (SF)