TY - JOUR
T1 - Thiaplakortone B attenuates RANKL‐induced NF‐κB and MAPK signaling and dampens OVX‐induced bone loss in mice
AU - Wang, Qingqing
AU - Chen, Delong
AU - Wang, Yining
AU - Dong, Chenlin
AU - Liu, Jian
AU - Chen, Kai
AU - Song, Fangming
AU - Wang, Chao
AU - Yuan, Jinbo
AU - Davis, Rohan A.
AU - Kuek, Vincent
AU - Jin, Haiming
AU - Xu, Jiake
N1 - Funding Information:
The authors acknowledge the support from the Australian National Health and Medical Research Council , Australia (NHMRC, Grant No. 1107828, 1027932, 1127156, 1024314). This study was also funded by the National Natural Science Foundation of China , china (Grant No. 82102313 , 81603641 , 81774339 , 81704098 ), the Natural Science Fund of Zhejiang Province , China (Grant No. LQ21H060009 ), Guangdong Provincial Science and Technology Project , China (Grant No. 2017A020213030 ) and 2019 Key Research of Guangzhou University of Chinese Medicine , china (Grant No. XK201912 ). RAD acknowledges the Nature Bankbiota repository ( https://www.griffith.edu.au/institute-drug-discovery/unique-resources/naturebank ) from which TPA and TPB were originally isolated. Compounds Australia ( https://www.griffith.edu.au/griffith-sciences/compounds-australia ) is acknowledged for curating the Davis Open Access Natural Product Library from which all the thiaplakortone derivatives were sourced [62,63] . We acknowledge the facilities and technical assistance of the Centre for Microscopy, Characterization & Analysis, the University of Western Australia. Qingqing Wang, Fangming Song and Delong Chen were visiting scholars to UWA.
Funding Information:
The authors acknowledge the support from the Australian National Health and Medical Research Council, Australia (NHMRC, Grant No. 1107828, 1027932, 1127156, 1024314). This study was also funded by the National Natural Science Foundation of China, china (Grant No. 82102313, 81603641, 81774339, 81704098), the Natural Science Fund of Zhejiang Province, China (Grant No. LQ21H060009), Guangdong Provincial Science and Technology Project, China (Grant No. 2017A020213030) and 2019 Key Research of Guangzhou University of Chinese Medicine, china (Grant No. XK201912). RAD acknowledges the Nature Bankbiota repository (https://www.griffith.edu.au/institute-drug-discovery/unique-resources/naturebank) from which TPA and TPB were originally isolated. Compounds Australia (https://www.griffith.edu.au/griffith-sciences/compounds-australia) is acknowledged for curating the Davis Open Access Natural Product Library from which all the thiaplakortone derivatives were sourced [62,63]. We acknowledge the facilities and technical assistance of the Centre for Microscopy, Characterization & Analysis, the University of Western Australia. Qingqing Wang, Fangming Song and Delong Chen were visiting scholars to UWA. Data are contained within the article or supplementary files.
Publisher Copyright:
© 2022 The Authors
PY - 2022/10
Y1 - 2022/10
N2 - Osteoclasts play an important role in maintaining the relative stability of bone mass. Abnormal number and function of osteoclasts are closely related to osteoporosis and osteolytic diseases. Thiaplakortone B (TPB), a natural compound derived from the Great Barrier Reef sponge Plakortis lita, has been reported to inhibit the growth of the malaria parasite, Plasmodium falciparum, but its effect on osteoclastogenesis has not been previously investigated. In our study, we found that TPB suppresses the receptor activator of nuclear factor‐κB (NF-κB) ligand (RANKL)-induced osteoclast formation and resorption activity by tartrate‐resistant acid phosphatase (TRAcP) staining, immunofluorescence staining of F-actin belts and hydroxyapatite resorption assay. Furthermore, using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis, we discovered that TPB inhibits osteoclast-specific genes and proteins expression. Mechanistically, TPB blocks multiple upstream pathways including calcium oscillation, NF‐κB, mitogen-activated protein kinase (MAPK) and nuclear factor of activated T cells 1(NFATc1) signaling pathways. In vivo, TPB could dampen bone loss in an ovariectomy (OVX) mouse model by micro-CT assessment and histological staining. Therefore, TPB may serve as a potential therapeutic candidate for the treatment of osteoporosis and osteolysis.
AB - Osteoclasts play an important role in maintaining the relative stability of bone mass. Abnormal number and function of osteoclasts are closely related to osteoporosis and osteolytic diseases. Thiaplakortone B (TPB), a natural compound derived from the Great Barrier Reef sponge Plakortis lita, has been reported to inhibit the growth of the malaria parasite, Plasmodium falciparum, but its effect on osteoclastogenesis has not been previously investigated. In our study, we found that TPB suppresses the receptor activator of nuclear factor‐κB (NF-κB) ligand (RANKL)-induced osteoclast formation and resorption activity by tartrate‐resistant acid phosphatase (TRAcP) staining, immunofluorescence staining of F-actin belts and hydroxyapatite resorption assay. Furthermore, using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis, we discovered that TPB inhibits osteoclast-specific genes and proteins expression. Mechanistically, TPB blocks multiple upstream pathways including calcium oscillation, NF‐κB, mitogen-activated protein kinase (MAPK) and nuclear factor of activated T cells 1(NFATc1) signaling pathways. In vivo, TPB could dampen bone loss in an ovariectomy (OVX) mouse model by micro-CT assessment and histological staining. Therefore, TPB may serve as a potential therapeutic candidate for the treatment of osteoporosis and osteolysis.
KW - MAPK
KW - Marine natural product
KW - NF‐κB
KW - Osteoclastogenesis
KW - Osteoporosis
KW - Thiaplakortone B
UR - http://www.scopus.com/inward/record.url?scp=85137280061&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2022.113622
DO - 10.1016/j.biopha.2022.113622
M3 - Article
C2 - 36081291
AN - SCOPUS:85137280061
VL - 154
JO - Biomedicine & pharmacotherapy
JF - Biomedicine & pharmacotherapy
SN - 0753-3322
M1 - 113622
ER -
