Thiaplakortone B attenuates RANKL‐induced NF‐κB and MAPK signaling and dampens OVX‐induced bone loss in mice
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 be...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222010113 |
| _version_ | 1798003176380563456 |
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| author | Qingqing Wang Delong Chen Yining Wang Chenlin Dong Jian Liu Kai Chen Fangming Song Chao Wang Jinbo Yuan Rohan A. Davis Vincent Kuek Haiming Jin Jiake Xu |
| author_facet | Qingqing Wang Delong Chen Yining Wang Chenlin Dong Jian Liu Kai Chen Fangming Song Chao Wang Jinbo Yuan Rohan A. Davis Vincent Kuek Haiming Jin Jiake Xu |
| author_sort | Qingqing Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T12:03:45Z |
| format | Article |
| id | doaj.art-227ad4820b88454781063235227d0673 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-11T12:03:45Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-227ad4820b88454781063235227d06732022-12-22T04:24:47ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-10-01154113622Thiaplakortone B attenuates RANKL‐induced NF‐κB and MAPK signaling and dampens OVX‐induced bone loss in miceQingqing Wang0Delong Chen1Yining Wang2Chenlin Dong3Jian Liu4Kai Chen5Fangming Song6Chao Wang7Jinbo Yuan8Rohan A. Davis9Vincent Kuek10Haiming Jin11Jiake Xu12Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang 310016, China; School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, AustraliaSchool of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, AustraliaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaSchool of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, AustraliaResearch Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, 530021, ChinaSchool of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, AustraliaSchool of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, AustraliaGriffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Queensland, 4111, AustraliaSchool of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia; Corresponding author.School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia; The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Corresponding author at: School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia.Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang 310016, China; School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia; Corresponding author at: Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang 310016, China.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.http://www.sciencedirect.com/science/article/pii/S0753332222010113Marine natural productThiaplakortone BOsteoclastogenesisNF‐κBMAPKOsteoporosis |
| spellingShingle | Qingqing Wang Delong Chen Yining Wang Chenlin Dong Jian Liu Kai Chen Fangming Song Chao Wang Jinbo Yuan Rohan A. Davis Vincent Kuek Haiming Jin Jiake Xu Thiaplakortone B attenuates RANKL‐induced NF‐κB and MAPK signaling and dampens OVX‐induced bone loss in mice Biomedicine & Pharmacotherapy Marine natural product Thiaplakortone B Osteoclastogenesis NF‐κB MAPK Osteoporosis |
| title | Thiaplakortone B attenuates RANKL‐induced NF‐κB and MAPK signaling and dampens OVX‐induced bone loss in mice |
| title_full | Thiaplakortone B attenuates RANKL‐induced NF‐κB and MAPK signaling and dampens OVX‐induced bone loss in mice |
| title_fullStr | Thiaplakortone B attenuates RANKL‐induced NF‐κB and MAPK signaling and dampens OVX‐induced bone loss in mice |
| title_full_unstemmed | Thiaplakortone B attenuates RANKL‐induced NF‐κB and MAPK signaling and dampens OVX‐induced bone loss in mice |
| title_short | Thiaplakortone B attenuates RANKL‐induced NF‐κB and MAPK signaling and dampens OVX‐induced bone loss in mice |
| title_sort | thiaplakortone b attenuates rankl induced nf κb and mapk signaling and dampens ovx induced bone loss in mice |
| topic | Marine natural product Thiaplakortone B Osteoclastogenesis NF‐κB MAPK Osteoporosis |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222010113 |
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