Anemoside B4 attenuates RANKL-induced osteoclastogenesis by upregulating Nrf2 and dampens ovariectomy-induced bone loss
Increased numbers and functional overactivity of osteoclasts are the pathological basis for bone loss diseases such as osteoporosis, which are characterized by cortical bone thinning, decreased trabecular bone quantity, and reduced bone mineral density. Effective inhibition of osteoclast formation a...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-11-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223012520 |
| _version_ | 1797660566152544256 |
|---|---|
| author | Zhen Cao Xuben Niu Maihuan Wang Siwang Yu Mingkun Wang Silong Mu Chuan Liu Yaxi Wang |
| author_facet | Zhen Cao Xuben Niu Maihuan Wang Siwang Yu Mingkun Wang Silong Mu Chuan Liu Yaxi Wang |
| author_sort | Zhen Cao |
| collection | DOAJ |
| description | Increased numbers and functional overactivity of osteoclasts are the pathological basis for bone loss diseases such as osteoporosis, which are characterized by cortical bone thinning, decreased trabecular bone quantity, and reduced bone mineral density. Effective inhibition of osteoclast formation and bone resorption are important means of treating such skeletal diseases. Anemoside B4 (AB4), the main active component of Pulsatilla chinensis, possesses a wide range of anti-inflammatory and immunoregulatory effects. However, its effect and mechanism in osteoclast differentiation remain unclear. In this study, we found through tartrate-resistant acidic phosphatase (TRAcP) staining and immunofluorescence staining that AB4 inhibited the differentiation, fusion, and bone-resorption functions of osteoclasts induced by receptor activator of nuclear factor κB ligand (RANKL) in vitro. Additionally, real time PCR (RT-qPCR) and western blot analysis showed AB4 downregulated the expression of osteoclast marker genes, including Nfatc1, Fos, and Ctsk, while upregulating Nrf2 expression. AB4 (5 mg/kg) alleviated bone loss in ovariectomized mice by inhibiting osteoclast formation. Furthermore, the knockout of Nrf2 weakened the inhibitory effects of AB4 on osteoclast formation and related gene expression. In summary, the results suggest AB4 can inhibit osteoclast differentiation and function by activating Nrf2 and indicate AB4 may be a candidate drug for osteoporosis. |
| first_indexed | 2024-03-11T18:31:45Z |
| format | Article |
| id | doaj.art-413543406f9d437d97857e1157840892 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T18:31:45Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-413543406f9d437d97857e11578408922023-10-13T11:02:40ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-11-01167115454Anemoside B4 attenuates RANKL-induced osteoclastogenesis by upregulating Nrf2 and dampens ovariectomy-induced bone lossZhen Cao0Xuben Niu1Maihuan Wang2Siwang Yu3Mingkun Wang4Silong Mu5Chuan Liu6Yaxi Wang7Department of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou 511442, ChinaDepartment of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou 511442, ChinaDepartment of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Molecular and Cellular Pharmacology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, ChinaDepartment of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, ChinaDepartment of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Orthopedic, The Seventh Medical Centre, Chinese PLA General Hospital, Beijing 100700, China; Corresponding authors.Department of Emergency, The Seventh Medical Centre, Chinese PLA General Hospital, Beijing 100700, China; Corresponding authors.Increased numbers and functional overactivity of osteoclasts are the pathological basis for bone loss diseases such as osteoporosis, which are characterized by cortical bone thinning, decreased trabecular bone quantity, and reduced bone mineral density. Effective inhibition of osteoclast formation and bone resorption are important means of treating such skeletal diseases. Anemoside B4 (AB4), the main active component of Pulsatilla chinensis, possesses a wide range of anti-inflammatory and immunoregulatory effects. However, its effect and mechanism in osteoclast differentiation remain unclear. In this study, we found through tartrate-resistant acidic phosphatase (TRAcP) staining and immunofluorescence staining that AB4 inhibited the differentiation, fusion, and bone-resorption functions of osteoclasts induced by receptor activator of nuclear factor κB ligand (RANKL) in vitro. Additionally, real time PCR (RT-qPCR) and western blot analysis showed AB4 downregulated the expression of osteoclast marker genes, including Nfatc1, Fos, and Ctsk, while upregulating Nrf2 expression. AB4 (5 mg/kg) alleviated bone loss in ovariectomized mice by inhibiting osteoclast formation. Furthermore, the knockout of Nrf2 weakened the inhibitory effects of AB4 on osteoclast formation and related gene expression. In summary, the results suggest AB4 can inhibit osteoclast differentiation and function by activating Nrf2 and indicate AB4 may be a candidate drug for osteoporosis.http://www.sciencedirect.com/science/article/pii/S0753332223012520Anemoside B4OsteoclastogenesisBone resorptionNrf2Osteoporosis |
| spellingShingle | Zhen Cao Xuben Niu Maihuan Wang Siwang Yu Mingkun Wang Silong Mu Chuan Liu Yaxi Wang Anemoside B4 attenuates RANKL-induced osteoclastogenesis by upregulating Nrf2 and dampens ovariectomy-induced bone loss Biomedicine & Pharmacotherapy Anemoside B4 Osteoclastogenesis Bone resorption Nrf2 Osteoporosis |
| title | Anemoside B4 attenuates RANKL-induced osteoclastogenesis by upregulating Nrf2 and dampens ovariectomy-induced bone loss |
| title_full | Anemoside B4 attenuates RANKL-induced osteoclastogenesis by upregulating Nrf2 and dampens ovariectomy-induced bone loss |
| title_fullStr | Anemoside B4 attenuates RANKL-induced osteoclastogenesis by upregulating Nrf2 and dampens ovariectomy-induced bone loss |
| title_full_unstemmed | Anemoside B4 attenuates RANKL-induced osteoclastogenesis by upregulating Nrf2 and dampens ovariectomy-induced bone loss |
| title_short | Anemoside B4 attenuates RANKL-induced osteoclastogenesis by upregulating Nrf2 and dampens ovariectomy-induced bone loss |
| title_sort | anemoside b4 attenuates rankl induced osteoclastogenesis by upregulating nrf2 and dampens ovariectomy induced bone loss |
| topic | Anemoside B4 Osteoclastogenesis Bone resorption Nrf2 Osteoporosis |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223012520 |
| work_keys_str_mv | AT zhencao anemosideb4attenuatesranklinducedosteoclastogenesisbyupregulatingnrf2anddampensovariectomyinducedboneloss AT xubenniu anemosideb4attenuatesranklinducedosteoclastogenesisbyupregulatingnrf2anddampensovariectomyinducedboneloss AT maihuanwang anemosideb4attenuatesranklinducedosteoclastogenesisbyupregulatingnrf2anddampensovariectomyinducedboneloss AT siwangyu anemosideb4attenuatesranklinducedosteoclastogenesisbyupregulatingnrf2anddampensovariectomyinducedboneloss AT mingkunwang anemosideb4attenuatesranklinducedosteoclastogenesisbyupregulatingnrf2anddampensovariectomyinducedboneloss AT silongmu anemosideb4attenuatesranklinducedosteoclastogenesisbyupregulatingnrf2anddampensovariectomyinducedboneloss AT chuanliu anemosideb4attenuatesranklinducedosteoclastogenesisbyupregulatingnrf2anddampensovariectomyinducedboneloss AT yaxiwang anemosideb4attenuatesranklinducedosteoclastogenesisbyupregulatingnrf2anddampensovariectomyinducedboneloss |