Extract of <i>Curculigo capitulata</i> Ameliorates Postmenopausal Osteoporosis by Promoting Osteoblast Proliferation and Differentiation
Postmenopausal osteoporosis (PMOP) is a bone disease characterized by bone thinning and an increased risk of fractures due to estrogen deficiency. Current PMOP therapies often result in adverse side effects. The traditional medicinal plant <i>Curculigo capitulata</i> is commonly used to...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/13/23/2028 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846124367087403008 |
|---|---|
| author | Ying Wang Xueru Wang Kaijin Wang Weiwei Qin Ning Li |
| author_facet | Ying Wang Xueru Wang Kaijin Wang Weiwei Qin Ning Li |
| author_sort | Ying Wang |
| collection | DOAJ |
| description | Postmenopausal osteoporosis (PMOP) is a bone disease characterized by bone thinning and an increased risk of fractures due to estrogen deficiency. Current PMOP therapies often result in adverse side effects. The traditional medicinal plant <i>Curculigo capitulata</i> is commonly used to strengthen bones and support kidney function, but its role in treating PMOP is not well understood. This study aims to investigate the therapeutic effects of the total extract of <i>Curculigo capitulata</i> (Eocc) on PMOP and to explore the underlying mechanisms. The major components of the extract were identified using HPLC. Transcriptomics was employed to predict potential targets. An osteogenic differentiation model of MC3T3-E1 cells was used in vitro. The osteogenic potential of the Eocc was assessed through CCK-8 cell viability assays, alkaline phosphatase (ALP) staining, Alizarin Red staining, Western blotting, and qPCR. MCF-7 and HEK-293 cells were utilized to evaluate the estrogen-like activity of Eocc. Apoptosis rates were detected by flow cytometry. In vivo, a bilateral ovariectomized mouse model of PMOP was used to further validate the in vitro findings through histopathological analysis and WB results. The results demonstrated that the Eocc promoted the proliferation of MC3T3-E1 cells, increased ALP activity, and stimulated the formation of osteogenic mineralized nodules. It also upregulated the expression of osteogenic markers (Runx2, OCN, OPN, and BSP) at both the protein and mRNA levels. The Eocc induced the activation of ERα both in vitro and in vivo, initiating the Src/PI3K/AKT signaling pathway, leading to the phosphorylation of GSK3β and subsequent osteogenesis. The activation of this pathway also stimulated the phosphorylation of mTOR and p70S6K while downregulating cleaved caspase-3 and caspase-9. Additionally, the Eocc reduced apoptosis during osteogenic differentiation and promoted cell proliferation. These findings suggest that the Eocc facilitates osteoblast proliferation and differentiation, improving bone integrity in PMOP mice, and may represent a promising therapeutic candidate for managing PMOP. |
| format | Article |
| id | doaj-art-735d5c1516d54f1489abf7c2846916ee |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-735d5c1516d54f1489abf7c2846916ee2024-12-13T16:24:21ZengMDPI AGCells2073-44092024-12-011323202810.3390/cells13232028Extract of <i>Curculigo capitulata</i> Ameliorates Postmenopausal Osteoporosis by Promoting Osteoblast Proliferation and DifferentiationYing Wang0Xueru Wang1Kaijin Wang2Weiwei Qin3Ning Li4Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaPostmenopausal osteoporosis (PMOP) is a bone disease characterized by bone thinning and an increased risk of fractures due to estrogen deficiency. Current PMOP therapies often result in adverse side effects. The traditional medicinal plant <i>Curculigo capitulata</i> is commonly used to strengthen bones and support kidney function, but its role in treating PMOP is not well understood. This study aims to investigate the therapeutic effects of the total extract of <i>Curculigo capitulata</i> (Eocc) on PMOP and to explore the underlying mechanisms. The major components of the extract were identified using HPLC. Transcriptomics was employed to predict potential targets. An osteogenic differentiation model of MC3T3-E1 cells was used in vitro. The osteogenic potential of the Eocc was assessed through CCK-8 cell viability assays, alkaline phosphatase (ALP) staining, Alizarin Red staining, Western blotting, and qPCR. MCF-7 and HEK-293 cells were utilized to evaluate the estrogen-like activity of Eocc. Apoptosis rates were detected by flow cytometry. In vivo, a bilateral ovariectomized mouse model of PMOP was used to further validate the in vitro findings through histopathological analysis and WB results. The results demonstrated that the Eocc promoted the proliferation of MC3T3-E1 cells, increased ALP activity, and stimulated the formation of osteogenic mineralized nodules. It also upregulated the expression of osteogenic markers (Runx2, OCN, OPN, and BSP) at both the protein and mRNA levels. The Eocc induced the activation of ERα both in vitro and in vivo, initiating the Src/PI3K/AKT signaling pathway, leading to the phosphorylation of GSK3β and subsequent osteogenesis. The activation of this pathway also stimulated the phosphorylation of mTOR and p70S6K while downregulating cleaved caspase-3 and caspase-9. Additionally, the Eocc reduced apoptosis during osteogenic differentiation and promoted cell proliferation. These findings suggest that the Eocc facilitates osteoblast proliferation and differentiation, improving bone integrity in PMOP mice, and may represent a promising therapeutic candidate for managing PMOP.https://www.mdpi.com/2073-4409/13/23/2028<i>Curculigo capitulata</i>ERαosteoblast proliferation and differentiationPMOPPI3K/AKT |
| spellingShingle | Ying Wang Xueru Wang Kaijin Wang Weiwei Qin Ning Li Extract of <i>Curculigo capitulata</i> Ameliorates Postmenopausal Osteoporosis by Promoting Osteoblast Proliferation and Differentiation Cells <i>Curculigo capitulata</i> ERα osteoblast proliferation and differentiation PMOP PI3K/AKT |
| title | Extract of <i>Curculigo capitulata</i> Ameliorates Postmenopausal Osteoporosis by Promoting Osteoblast Proliferation and Differentiation |
| title_full | Extract of <i>Curculigo capitulata</i> Ameliorates Postmenopausal Osteoporosis by Promoting Osteoblast Proliferation and Differentiation |
| title_fullStr | Extract of <i>Curculigo capitulata</i> Ameliorates Postmenopausal Osteoporosis by Promoting Osteoblast Proliferation and Differentiation |
| title_full_unstemmed | Extract of <i>Curculigo capitulata</i> Ameliorates Postmenopausal Osteoporosis by Promoting Osteoblast Proliferation and Differentiation |
| title_short | Extract of <i>Curculigo capitulata</i> Ameliorates Postmenopausal Osteoporosis by Promoting Osteoblast Proliferation and Differentiation |
| title_sort | extract of i curculigo capitulata i ameliorates postmenopausal osteoporosis by promoting osteoblast proliferation and differentiation |
| topic | <i>Curculigo capitulata</i> ERα osteoblast proliferation and differentiation PMOP PI3K/AKT |
| url | https://www.mdpi.com/2073-4409/13/23/2028 |
| work_keys_str_mv | AT yingwang extractoficurculigocapitulataiamelioratespostmenopausalosteoporosisbypromotingosteoblastproliferationanddifferentiation AT xueruwang extractoficurculigocapitulataiamelioratespostmenopausalosteoporosisbypromotingosteoblastproliferationanddifferentiation AT kaijinwang extractoficurculigocapitulataiamelioratespostmenopausalosteoporosisbypromotingosteoblastproliferationanddifferentiation AT weiweiqin extractoficurculigocapitulataiamelioratespostmenopausalosteoporosisbypromotingosteoblastproliferationanddifferentiation AT ningli extractoficurculigocapitulataiamelioratespostmenopausalosteoporosisbypromotingosteoblastproliferationanddifferentiation |