Effects of Triterpene Soyasapogenol B from Arachis hypogaea (Peanut) on Differentiation, Mineralization, Autophagy, and Necroptosis in Pre-Osteoblasts
Abstract
:1. Introduction
2. Results
2.1. Isolation and Identification of SoyB Purified from A. hypogaea
2.2. SoyB Enhances Osteogenic Activity and Maturation
2.3. SoyB Enhances the Nuclear Expression of RUNX2 and Phosphorylation of Smad1/5/8 and JNK
2.4. SoyB Does Not Influences Autophagy and Necroptosis during Osteoblast Differentiation
2.5. SoyB Enhances Adhesion and Cell Transmigration during Osteoblast Differentiation
3. Discussion
4. Materials and Methods
4.1. General Experimental Procedures of Plant Material and Purity
4.2. Cell Culture and Osteoblast Differentiation
4.3. Cell Proliferation Assay
4.4. Early and Late Osteogenic Activity Analyses
4.5. Western Blot Analysis
4.6. Immunofluorescence
4.7. Autophagosome Formation Assay
4.8. Transmigration Assay
4.9. Cell Adhesion Assay
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ALP | Alkaline phosphatase |
ARS | Alizarin Red S |
β-GP | β-glycerophosphate |
ECM | Extracellular matrix |
L-AA | L-ascorbic acid |
LC3 | Microtubule associated protein light chain 3 |
MAPKs | Mitogen-activated protein kinases |
MMP | Matrix metalloproteinase |
MSCs | Mesenchymal stem cells |
MTT | 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) |
OS | Osteogenic supplement medium |
RUNX2 | Runt-related transcription factor 2 |
SoyB | Soyasapogenol B |
References
- Kobayashi, T.; Kronenberg, H.M. Overview of Skeletal Development. Methods Mol. Biol. 2021, 2230, 3–16. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Zhang, T.; Jiang, M.; Yin, X.; Luo, X.; Sun, H. Effect of the immune responses induced by implants in a integrated three-dimensional micro-nano topography on osseointegration. J. Biomed. Mater. Res. Part A 2021, 109, 1429–1440. [Google Scholar] [CrossRef]
- Park, K.-R.; Kim, S.; Cho, M.; Yun, H.-M. Limonoid Triterpene, Obacunone Increases Runt-Related Transcription Factor 2 to Promote Osteoblast Differentiation and Function. Int. J. Mol. Sci. 2021, 22, 2483. [Google Scholar] [CrossRef]
- Khotib, J.; Gani, M.A.; Budiatin, A.S.; Lestari, M.L.A.D.; Rahadiansyah, E.; Ardianto, C. Signaling Pathway and Transcriptional Regulation in Osteoblasts during Bone Healing: Direct Involvement of Hydroxyapatite as a Biomaterial. Pharmaceuticals 2021, 14, 615. [Google Scholar] [CrossRef] [PubMed]
- Park, K.-R.; Lee, J.; Cho, M.; Hong, J.; Yun, H.-M. Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules. Int. J. Mol. Sci. 2021, 22, 6899. [Google Scholar] [CrossRef] [PubMed]
- Deng, T.; Zhang, W.; Zhang, Y.; Zhang, M.; Huan, Z.; Yu, C.; Zhang, X.; Wang, Y.; Xu, J. Thyroid-stimulating hormone decreases the risk of osteoporosis by regulating osteoblast proliferation and differentiation. BMC Endocr. Disord. 2021, 21, 49. [Google Scholar] [CrossRef] [PubMed]
- Shalehin, N.; Hosoya, A.; Takebe, H.; Hasan, M.R.; Irie, K. Boric acid inhibits alveolar bone loss in rat experimental periodontitis through diminished bone resorption and enhanced osteoblast formation. J. Dent. Sci 2020, 15, 437–444. [Google Scholar] [CrossRef]
- Martiniakova, M.; Babikova, M.; Omelka, R. Pharmacological agents and natural compounds: Available treatments for osteoporosis. J. Physiol. Pharmacol. 2021, 71, 307–320. [Google Scholar] [CrossRef]
- Akram, N.A.; Shafiq, F.; Ashraf, M. Peanut (Arachis hypogaea L.): A Prospective Legume Crop to Offer Multiple Health Benefits under Changing Climate. Compr. Rev. Food Sci. Food Saf. 2018, 17, 1325–1338. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, K.H.; Lai, Y.H.; Chang, J.C.; Ko, T.F.; Shyu, S.L.; Chiou, R.Y.Y. Germination of peanut kernels to enhance resveratrol biosynthesis and prepare sprouts as a functional vegetable. J. Agric. Food Chem. 2005, 53, 242–246. [Google Scholar] [CrossRef]
- Lertkaeo, P.; Limmongkon, A.; Srikummool, M.; Boonsong, T.; Supanpaiboon, W.; Surangkul, D. Antioxidative and neuroprotective activities of peanut sprout extracts against oxidative stress in SK-N-SH cells. Asian Pac. J. Trop. Biomed. 2017, 7, 64–69. [Google Scholar] [CrossRef] [Green Version]
- Sasaki, K.; Minowa, N.; Kuzuhara, H.; Nishiyama, S. Preventive effects of soyasapogenol B derivatives on liver injury in a concanavalin A-induced hepatitis model. Bioorganic Med. Chem. 2005, 13, 4900–4911. [Google Scholar] [CrossRef]
- Kinjo, J.; Hirakawa, T.; Tsuchihashi, R.; Nagao, T.; Okawa, M.; Nohara, T.; Okabe, H. Hepatoprotective constituents in plants. 14. Effects of soyasapogenol B, sophoradiol, and their glucuronides on the cytotoxicity of tert-butyl hydroperoxide to HepG2 cells. Biol. Pharm. Bull. 2003, 26, 1357–1360. [Google Scholar] [CrossRef] [Green Version]
- Zhang, W.; Popovich, D.G. Effect of soyasapogenol A and soyasapogenol B concentrated extracts on HEP-G2 cell proliferation and apoptosis. J. Agric. Food Chem. 2008, 56, 2603–2608. [Google Scholar] [CrossRef] [PubMed]
- Choi, C.W.; Choi, S.W.; Kim, H.J.; Lee, K.S.; Kim, S.H.; Kim, S.L.; Do, S.H.; Seo, W.D. Germinated soy germ with increased soyasaponin Ab improves BMP-2-induced bone formation and protects against in vivo bone loss in osteoporosis. Sci. Rep. 2018, 8, 12970. [Google Scholar] [CrossRef]
- Ge, C.; Xiao, G.; Jiang, D.; Yang, Q.; Hatch, N.E.; Roca, H.; Franceschi, R.T. Identification and functional characterization of ERK/MAPK phosphorylation sites in the Runx2 transcription factor. J. Biol. Chem. 2009, 284, 32533–32543. [Google Scholar] [CrossRef] [Green Version]
- Greenblatt, M.B.; Shim, J.H.; Glimcher, L.H. Mitogen-activated protein kinase pathways in osteoblasts. Annu. Rev. Cell Dev. Biol. 2013, 29, 63–79. [Google Scholar] [CrossRef]
- Gaur, T.; Lengner, C.J.; Hovhannisyan, H.; Bhat, R.A.; Bodine, P.V.; Komm, B.S.; Javed, A.; van Wijnen, A.J.; Stein, J.L.; Stein, G.S.; et al. Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J. Biol. Chem. 2005, 280, 33132–33140. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Phimphilai, M.; Zhao, Z.; Boules, H.; Roca, H.; Franceschi, R.T. BMP signaling is required for RUNX2-dependent induction of the osteoblast phenotype. J. Bone Miner. Res. 2006, 21, 637–646. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Darcy, A.; Meltzer, M.; Miller, J.; Lee, S.; Chappell, S.; Donck, K.V.; Montano, M. A novel library screen identifies immunosuppressors that promote osteoblast differentiation. Bone 2012, 50, 1294–1303. [Google Scholar] [CrossRef] [Green Version]
- Liu, F.; Fang, F.; Yuan, H.; Yang, D.; Chen, Y.; Williams, L.; Goldstein, S.A.; Krebsbach, P.H.; Guan, J.L. Suppression of autophagy by FIP200 deletion leads to osteopenia in mice through the inhibition of osteoblast terminal differentiation. J. Bone Miner. Res. 2013, 28, 2414–2430. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, I.R.; Kim, S.E.; Baek, H.S.; Kim, B.J.; Kim, C.H.; Chung, I.K.; Park, B.S.; Shin, S.H. The role of kaempferol-induced autophagy on differentiation and mineralization of osteoblastic MC3T3-E1 cells. BMC Complement. Altern. Med. 2016, 16, 333. [Google Scholar] [CrossRef] [Green Version]
- Wang, L.; Yun, L.; Wang, X.; Sha, L.; Sui, Y.; Zhang, H. Endoplasmic reticulum stress triggered by Soyasapogenol B promotes apoptosis and autophagy in colorectal cancer. Life Sci. 2019, 218, 16–24. [Google Scholar] [CrossRef]
- Cho, Y.S.; Park, S.Y. Harnessing of Programmed Necrosis for Fighting against Cancers. Biomol. Ther. 2014, 22, 167–175. [Google Scholar] [CrossRef] [Green Version]
- Hoang, V.H.; Apostolova, P.; Dostalova, J.; Pudil, F.; Pokorny, J. Antioxidant Activity of Peanut Skin Extracts from Conventional and High-Oleic Peanuts. Czech J. Food Sci. 2008, 26, 447–457. [Google Scholar] [CrossRef] [Green Version]
- Orimo, H. The mechanism of mineralization and the role of alkaline phosphatase in health and disease. J. Nippon Med. Sch. 2010, 77, 4–12. [Google Scholar] [CrossRef] [Green Version]
- Golub, E.E.; Harrison, G.; Taylor, A.G.; Camper, S.; Shapiro, I.M. The role of alkaline phosphatase in cartilage mineralization. Bone Miner. 1992, 17, 273–278. [Google Scholar] [CrossRef]
- Yun, H.M.; Park, K.R.; Hong, J.T.; Kim, E.C. Peripheral serotonin-mediated system suppresses bone development and regeneration via serotonin 6 G-protein-coupled receptor. Sci. Rep. 2016, 6, 30985. [Google Scholar] [CrossRef]
- Wennberg, C.; Hessle, L.; Lundberg, P.; Mauro, S.; Narisawa, S.; Lerner, U.H.; Millan, J.L. Functional characterization of osteoblasts and osteoclasts from alkaline phosphatase knockout mice. J. Bone Miner. Res. 2000, 15, 1879–1888. [Google Scholar] [CrossRef]
- Huang, R.L.; Yuan, Y.; Tu, J.; Zou, G.M.; Li, Q. Opposing TNF-alpha/IL-1beta- and BMP-2-activated MAPK signaling pathways converge on Runx2 to regulate BMP-2-induced osteoblastic differentiation. Cell Death Dis. 2014, 5, e1187. [Google Scholar] [CrossRef] [Green Version]
- Yun, H.M.; Park, K.R.; Quang, T.H.; Oh, H.; Hong, J.T.; Kim, Y.C.; Kim, E.C. 2,4,5-Trimethoxyldalbergiquinol promotes osteoblastic differentiation and mineralization via the BMP and Wnt/beta-catenin pathway. Cell Death Dis. 2015, 6, e1819. [Google Scholar] [CrossRef] [Green Version]
- Yang, S.; Guo, L.; Su, Y.; Wen, J.; Du, J.; Li, X.; Liu, Y.; Feng, J.; Xie, Y.; Bai, Y.; et al. Nitric oxide balances osteoblast and adipocyte lineage differentiation via the JNK/MAPK signaling pathway in periodontal ligament stem cells. Stem Cell Res. Ther. 2018, 9, 118. [Google Scholar] [CrossRef]
- Kusuyama, J.; Amir, M.S.; Albertson, B.G.; Bandow, K.; Ohnishi, T.; Nakamura, T.; Noguchi, K.; Shima, K.; Semba, I.; Matsuguchi, T. JNK inactivation suppresses osteogenic differentiation, but robustly induces osteopontin expression in osteoblasts through the induction of inhibitor of DNA binding 4 (Id4). FASEB J. 2019, 33, 7331–7347. [Google Scholar] [CrossRef]
- Xu, R.; Zhang, C.; Shin, D.Y.; Kim, J.M.; Lalani, S.; Li, N.; Yang, Y.S.; Liu, Y.; Eiseman, M.; Davis, R.J.; et al. c-Jun N-Terminal Kinases (JNKs) Are Critical Mediators of Osteoblast Activity In Vivo. J. Bone Miner. Res. 2017, 32, 1811–1815. [Google Scholar] [CrossRef] [Green Version]
- Fu, L.; Peng, S.; Wu, W.; Ouyang, Y.; Tan, D.; Fu, X. LncRNA HOTAIRM1 promotes osteogenesis by controlling JNK/AP-1 signalling-mediated RUNX2 expression. J. Cell. Mol. Med. 2019, 23, 7517–7524. [Google Scholar] [CrossRef] [Green Version]
- Li, W.; Zhang, S.; Liu, J.; Liu, Y.; Liang, Q. Vitamin K2 stimulates MC3T3E1 osteoblast differentiation and mineralization through autophagy induction. Mol. Med. Rep. 2019, 19, 3676–3684. [Google Scholar] [CrossRef]
- Tian, Q.; Qin, B.; Gu, Y.; Zhou, L.; Chen, S.; Zhang, S.; Han, Q.; Liu, Y.; Wu, X. ROS-Mediated Necroptosis Is Involved in Iron Overload-Induced Osteoblastic Cell Death. Oxidative Med. Cell. Longev. 2020, 2020, 1295382. [Google Scholar] [CrossRef]
- Shi, G.; Jia, P.; Chen, H.; Bao, L.; Feng, F.; Tang, H. Necroptosis occurs in osteoblasts during tumor necrosis factor-alpha stimulation and caspase-8 inhibition. Braz J. Med. Biol. Res. 2018, 52, e7844. [Google Scholar] [CrossRef]
- Guo, M.; Huang, Y.L.; Wu, Q.; Chai, L.; Jiang, Z.Z.; Zeng, Y.; Wan, S.R.; Tan, X.Z.; Long, Y.; Gu, J.L.; et al. Chronic Ethanol Consumption Induces Osteopenia via Activation of Osteoblast Necroptosis. Oxidative Med. Cell. Longev. 2021, 2021, 3027954. [Google Scholar] [CrossRef]
- Uusitalo, H.; Hiltunen, A.; Soderstrom, M.; Aro, H.T.; Vuorio, E. Expression of cathepsins B, H, K, L, and S and matrix metalloproteinases 9 and 13 during chondrocyte hypertrophy and endochondral ossification in mouse fracture callus. Calcif. Tissue Int. 2000, 67, 382–390. [Google Scholar] [CrossRef]
- Yamagiwa, H.; Tokunaga, K.; Hayami, T.; Hatano, H.; Uchida, M.; Endo, N.; Takahashi, H.E. Expression of metalloproteinase-13 (Collagenase-3) is induced during fracture healing in mice. Bone 1999, 25, 197–203. [Google Scholar] [CrossRef]
- Toriseva, M.; Laato, M.; Carpen, O.; Ruohonen, S.T.; Savontaus, E.; Inada, M.; Krane, S.M.; Kahari, V.M. MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability. PLoS ONE 2012, 7, e42596. [Google Scholar] [CrossRef]
- Sista, S.; Wen, C.; Hodgson, P.D.; Pande, G. Expression of cell adhesion and differentiation related genes in MC3T3 osteoblasts plated on titanium alloys: Role of surface properties. Mater. Sci. Eng. C Mater. Biol. Appl. 2013, 33, 1573–1582. [Google Scholar] [CrossRef]
- Wang, Z.; Li, Z.; Zhang, X.; Yu, Y.; Feng, Q.; Chen, J.; Xie, W. A bone substitute composed of polymethyl-methacrylate bone cement and Bio-Gene allogeneic bone promotes osteoblast viability, adhesion and differentiation. Biomed. Mater. Eng. 2021, 32, 29–37. [Google Scholar] [CrossRef]
- Pan, X.; Li, Y.; Abdullah, A.O.; Wang, W.; Qi, M.; Liu, Y. Micro/nano-hierarchical structured TiO2 coating on titanium by micro-arc oxidation enhances osteoblast adhesion and differentiation. R. Soc. Open Sci. 2019, 6, 182031. [Google Scholar] [CrossRef] [Green Version]
- Luo, F.; Hong, G.; Matsui, H.; Endo, K.; Wan, Q.; Sasaki, K. Initial osteoblast adhesion and subsequent differentiation on zirconia surfaces are regulated by integrins and heparin-sensitive molecule. Int. J. Nanomed. 2018, 13, 7657–7667. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ma, X.Y.; Feng, Y.F.; Wang, T.S.; Lei, W.; Li, X.; Zhou, D.P.; Wen, X.X.; Yu, H.L.; Xiang, L.B.; Wang, L. Involvement of FAK-mediated BMP-2/Smad pathway in mediating osteoblast adhesion and differentiation on nano-HA/chitosan composite coated titanium implant under diabetic conditions. Biomater. Sci. 2017, 6, 225–238. [Google Scholar] [CrossRef]
- Park, K.R.; Park, J.E.; Kim, B.; Kwon, I.K.; Hong, J.T.; Yun, H.M. Calycosin-7-O-beta-Glucoside Isolated from Astragalus membranaceus Promotes Osteogenesis and Mineralization in Human Mesenchymal Stem Cells. Int. J. Mol. Sci. 2021, 22, 11362. [Google Scholar] [CrossRef]
- Park, K.R.; Jeong, Y.; Lee, J.; Kwon, I.K.; Yun, H.M. Anti-tumor effects of jaceosidin on apoptosis, autophagy, and necroptosis in human glioblastoma multiforme. Am. J. Cancer Res. 2021, 11, 4919–4930. [Google Scholar]
- Park, K.R.; Leem, H.H.; Cho, M.; Kang, S.W.; Yun, H.M. Effects of the amide alkaloid piperyline on apoptosis, autophagy, and differentiation of pre-osteoblasts. Phytomedicine 2020, 79, 153347. [Google Scholar] [CrossRef]
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Yun, H.-M.; Lee, J.Y.; Kim, S.H.; Kwon, I.K.; Park, K.-R. Effects of Triterpene Soyasapogenol B from Arachis hypogaea (Peanut) on Differentiation, Mineralization, Autophagy, and Necroptosis in Pre-Osteoblasts. Int. J. Mol. Sci. 2022, 23, 8297. https://doi.org/10.3390/ijms23158297
Yun H-M, Lee JY, Kim SH, Kwon IK, Park K-R. Effects of Triterpene Soyasapogenol B from Arachis hypogaea (Peanut) on Differentiation, Mineralization, Autophagy, and Necroptosis in Pre-Osteoblasts. International Journal of Molecular Sciences. 2022; 23(15):8297. https://doi.org/10.3390/ijms23158297
Chicago/Turabian StyleYun, Hyung-Mun, Joon Yeop Lee, Soo Hyun Kim, Il Keun Kwon, and Kyung-Ran Park. 2022. "Effects of Triterpene Soyasapogenol B from Arachis hypogaea (Peanut) on Differentiation, Mineralization, Autophagy, and Necroptosis in Pre-Osteoblasts" International Journal of Molecular Sciences 23, no. 15: 8297. https://doi.org/10.3390/ijms23158297