Experimental study of resveratrol-solid lipid nanoparticles in promotion of osteogenic differentiation of bone marrow mesenchymal stem cells_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

XIONG Feng ^1,2,3 , YAO Cheng ^1,2,3 , ZHOU Liangshuang ^1,2,3 , LI Weifeng ^1,2 , WEI Bangguo ^3,4 ,  GUAN Jianzhong ^2,3 ,  MAO Yingji ^1,4

1. Bengbu Medical College, Bengbu Anhui, 233000, P. R. China;
2. Key Laboratory of Anhui Province for Tissue Transplantation, Bengbu Anhui, 233000, P. R. China;
3. Department of Orthopedics, the First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui, 233000, P. R. China;
4. School of Life Sciences, Bengbu Medical College, Bengbu Anhui, 233000, P. R. China;

Corresponding author：

GUAN Jianzhong, Email: guanjianzhong@bbmc.edu.cn; MAO Yingji, Email: myj123@bbmc.edu.cn

Keywords：

Resveratrol; solid lipid nanoparticles; bone marrow mesenchymal stem cells; osteogenic differentiation

DOI：

10.7507/1002-1892.202205009

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effect of solid lipid nanoparticles (SLNs) on enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro by resveratrol (Res), and provide a method for the treatment of bone homeostasis disorders. Methods Res-SLNs were prepared by high-temperature emulsification and low-temperature solidification method, and then the 2nd-3rd generation BMSCs from Sprague Dawley rat were co-cultured with different concentrations (0, 0.1, 1, 5, 10, 20 μmol/L) of Res and Res-SLNs. The effects of Res and Res-SLNs on the cell viability of BMSCs were detected by cell counting kit 8 (CCK-8) and live/dead cell staining; the effects of Res and Res-SLNs on the osteogenic differentiation of BMSCs were detected by alkaline phosphatase (ALP) staining and alizarin red S (ARS) staining after osteogenic differentiation induction, and the optimal concentration of Res-SLNs for gene detection was determined. Anti-osteocalcin (OCN) immunofluorescence staining and real-time fluorescent quantitative PCR (RT-qPCR) were used to detect the effect of Res and Res-SLNs on osteoblast-related genes (ALP and OCN) of BMSCs. Results Live/dead cell staining showed that there was no significant difference in the number of dead cells between Res and Res-SLNs groups; CCK-8 detection showed that the activity of BMSCs in Res group was significantly reduced at the concentration of 20 μmol/L (P<0.05), while Res-SLNs activity was not affected by Res concentration (P>0.05). After osteogenic differentiation, the staining intensity of ALP and ARS in both groups was dose-dependent. The percentage of ALP positive staining area and the percentage of mineralized nodule area in Res group and Res-SLNs group reached the maximum at the concentrations of 10 μmol/L and 1 μmol/L, respectively (P<0.05), and then decreased gradually; the most effective concentration of Res-SLNs was 1 μmol/L. The expression of OCN and the relative expression of ALP and OCN mRNA in Res-SLNs group were significantly higher than those in Res group (P<0.05). Conclusion Encapsulation of SLNs can improve the effect of Res on promoting osteogenesis, and achieve the best effect of osteogenic differentiation of BMSCs at a lower concentration, which is expected to be used in the treatment of bone homeostasis imbalance diseases.

Citation： XIONG Feng, YAO Cheng, ZHOU Liangshuang, LI Weifeng, WEI Bangguo, GUAN Jianzhong, MAO Yingji. Experimental study of resveratrol-solid lipid nanoparticles in promotion of osteogenic differentiation of bone marrow mesenchymal stem cells. Chinese Journal of Reparative and Reconstructive Surgery, 2022, 36(9): 1155-1165. doi: 10.7507/1002-1892.202205009 Copy

1.	Hasegawa T, Kikuta J, Sudo T, et al. Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1. Nat Immunol, 2019, 20(12): 1631-1643.
2.	Zainabadi K. Drugs targeting SIRT1, a new generation of therapeutics for osteoporosis and other bone related disorders? Pharmacol Res, 2019, 143: 97-105.
3.	Bellavia D, Dimarco E, Costa V, et al. Flavonoids in bone erosive diseases: Perspectives in osteoporosis treatment. Trends Endocrinol Metab, 2021, 32(2): 76-94.
4.	Zhang Y, Yang K, Yang J, et al. SENP3 suppresses osteoclastogenesis by de-conjugating SUMO2/3 from IRF8 in bone marrow-derived monocytes. Cell Rep, 2020, 30(6): 1951-1963.
5.	Gligorijević N, Radomirović M, Rajković A, et al. Fibrinogen increases resveratrol solubility and prevents it from oxidation. Foods, 2020, 9(6): 780. doi: 10.3390/foods9060780.
6.	Zhao XE, Yang Z, Zhang H, et al. Resveratrol promotes osteogenic differentiation of canine bone marrow mesenchymal stem cells through Wnt/Beta-catenin signaling pathway. Cell Reprogram, 2018, 20(6): 371-381.
7.	Xiong G, Yang Y, Guo M. Effect of resveratrol on abnormal bone remodeling and angiogenesis of subchondral bone in osteoarthritis. Int J Clin Exp Pathol, 2021, 14(4): 417-425.
8.	Wei B, Wang W, Liu X, et al. Gelatin methacrylate hydrogel scaffold carrying resveratrol-loaded solid lipid nanoparticles for enhancement of osteogenic differentiation of BMSCs and effective bone regeneration. Regen Biomater, 2021, 8(5): rbab044. doi: 10.1093/rb/rbab044.
9.	Griffin RJ, Avery E, Xia CQ. Predicting approximate clinically effective doses in oncology using preclinical efficacy and body surface area conversion: A retrospective analysis. Front Pharmacol, 2022, 13: 830972. doi: 10.3389/fphar.2022.830972.
10.	Li Q, Yang G, Xu H, et al. Effects of resveratrol supplementation on bone quality: a systematic review and meta-analysis of randomized controlled trials. BMC Complement Med Ther, 2021, 21(1): 214. doi: 10.1186/s12906-021-03381-4.
11.	Azizi M, Li Y, Kaul N, et al. Study of the physicochemical properties of fish oil solid lipid nanoparticle in the presence of palmitic acid and quercetin. J Agric Food Chem, 2019, 67(2): 671-679.
12.	Qushawy M, Prabahar K, Abd-Alhaseeb M, et al. Preparation and evaluation of carbamazepine solid lipid nanoparticle for alleviating seizure activity in pentylenetetrazole-kindled mice. Molecules, 2019, 24(21): 3971. doi: 10.3390/molecules24213971.
13.	Loureiro JA, Andrade S, Duarte A, et al. Resveratrol and grape extract-loaded solid lipid nanoparticles for the treatment of Alzheimer’s Disease. Molecules, 2017, 22(2): 277. doi: 10.3390/molecules22020277.
14.	Wang W, Zhou M, Xu Y, et al. Resveratrol-loaded TPGS-resveratrol-solid lipid nanoparticles for multidrug-resistant therapy of breast cancer: In vivo and in vitro study. Front Bioeng Biotechnol, 2021, 9: 762489. doi: 10.3389/fbioe.2021.762489.
15.	Zhou P, Xu P, Guan J, et al. Promoting 3D neuronal differentiation in hydrogel for spinal cord regeneration. Colloids Surf B Biointerfaces, 2020, 194: 111214. doi: 10.1016/j.colsurfb.2020.111214.
16.	刘翔宇, 王照东, 徐陈, 等. 载外源性TGF-β₁甲基丙烯酰化明胶复合支架促进颅骨缺损修复实验研究. 中国修复重建外科杂志, 2021, 35(7): 904-912.
17.	Zhou T, Yan Y, Zhao C, et al. Resveratrol improves osteogenic differentiation of senescent bone mesenchymal stem cells through inhibiting endogenous reactive oxygen species production via AMPK activation. Redox Rep, 2019, 24(1): 62-69.
18.	Moghanian A, Portillo-Lara R, Shirzaei Sani E, et al. Synthesis and characterization of osteoinductive visible light-activated adhesive composites with antimicrobial properties. J Tissue Eng Regen Med, 2020, 14(1): 66-81.
19.	Chen LZ, Yao L, Jiao MM, et al. Novel resveratrol-based flavonol derivatives: Synthesis and anti-inflammatory activity in vitro and in vivo. Eur J Med Chem, 2019, 175: 114-128.
20.	Parvez S, Karole A, Mudavath SL. Transport mechanism of hydroxy-propyl-beta-cyclodextrin modified solid lipid nanoparticles across human epithelial cells for the oral absorption of antileishmanial drugs. Biochim Biophys Acta Gen Subj, 2022, 1866(8): 130157. doi: 10.1016/j.bbagen.2022.130157.
21.	Dai Z, Li Y, Quarles LD, et al. Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation. Phytomedicine, 2007, 14(12): 806-814.
22.	Zhang W, Wang N, Yang M, et al. Periosteum and development of the tissue-engineered periosteum for guided bone regeneration. J Orthop Translat, 2022, 33: 41-54.
23.	Wu ZL, Zhao J, Xu R. Recent advances in oral nano-antibiotics for bacterial infection therapy. Int J Nanomedicine, 2020, 15: 9587-9610.
24.	Vishwakarma N, Jain A, Sharma R, et al. Lipid-based nanocarriers for lymphatic transportation. AAPS PharmSciTech, 2019, 20(2): 83. doi: 10.1208/s12249-019-1293-3.

1. Hasegawa T, Kikuta J, Sudo T, et al. Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1. Nat Immunol, 2019, 20(12): 1631-1643.
2. Zainabadi K. Drugs targeting SIRT1, a new generation of therapeutics for osteoporosis and other bone related disorders? Pharmacol Res, 2019, 143: 97-105.
3. Bellavia D, Dimarco E, Costa V, et al. Flavonoids in bone erosive diseases: Perspectives in osteoporosis treatment. Trends Endocrinol Metab, 2021, 32(2): 76-94.
4. Zhang Y, Yang K, Yang J, et al. SENP3 suppresses osteoclastogenesis by de-conjugating SUMO2/3 from IRF8 in bone marrow-derived monocytes. Cell Rep, 2020, 30(6): 1951-1963.
5. Gligorijević N, Radomirović M, Rajković A, et al. Fibrinogen increases resveratrol solubility and prevents it from oxidation. Foods, 2020, 9(6): 780. doi: 10.3390/foods9060780.
6. Zhao XE, Yang Z, Zhang H, et al. Resveratrol promotes osteogenic differentiation of canine bone marrow mesenchymal stem cells through Wnt/Beta-catenin signaling pathway. Cell Reprogram, 2018, 20(6): 371-381.
7. Xiong G, Yang Y, Guo M. Effect of resveratrol on abnormal bone remodeling and angiogenesis of subchondral bone in osteoarthritis. Int J Clin Exp Pathol, 2021, 14(4): 417-425.
8. Wei B, Wang W, Liu X, et al. Gelatin methacrylate hydrogel scaffold carrying resveratrol-loaded solid lipid nanoparticles for enhancement of osteogenic differentiation of BMSCs and effective bone regeneration. Regen Biomater, 2021, 8(5): rbab044. doi: 10.1093/rb/rbab044.
9. Griffin RJ, Avery E, Xia CQ. Predicting approximate clinically effective doses in oncology using preclinical efficacy and body surface area conversion: A retrospective analysis. Front Pharmacol, 2022, 13: 830972. doi: 10.3389/fphar.2022.830972.
10. Li Q, Yang G, Xu H, et al. Effects of resveratrol supplementation on bone quality: a systematic review and meta-analysis of randomized controlled trials. BMC Complement Med Ther, 2021, 21(1): 214. doi: 10.1186/s12906-021-03381-4.
11. Azizi M, Li Y, Kaul N, et al. Study of the physicochemical properties of fish oil solid lipid nanoparticle in the presence of palmitic acid and quercetin. J Agric Food Chem, 2019, 67(2): 671-679.
12. Qushawy M, Prabahar K, Abd-Alhaseeb M, et al. Preparation and evaluation of carbamazepine solid lipid nanoparticle for alleviating seizure activity in pentylenetetrazole-kindled mice. Molecules, 2019, 24(21): 3971. doi: 10.3390/molecules24213971.
13. Loureiro JA, Andrade S, Duarte A, et al. Resveratrol and grape extract-loaded solid lipid nanoparticles for the treatment of Alzheimer’s Disease. Molecules, 2017, 22(2): 277. doi: 10.3390/molecules22020277.
14. Wang W, Zhou M, Xu Y, et al. Resveratrol-loaded TPGS-resveratrol-solid lipid nanoparticles for multidrug-resistant therapy of breast cancer: In vivo and in vitro study. Front Bioeng Biotechnol, 2021, 9: 762489. doi: 10.3389/fbioe.2021.762489.
15. Zhou P, Xu P, Guan J, et al. Promoting 3D neuronal differentiation in hydrogel for spinal cord regeneration. Colloids Surf B Biointerfaces, 2020, 194: 111214. doi: 10.1016/j.colsurfb.2020.111214.
16. 刘翔宇, 王照东, 徐陈, 等. 载外源性TGF-β₁甲基丙烯酰化明胶复合支架促进颅骨缺损修复实验研究. 中国修复重建外科杂志, 2021, 35(7): 904-912.
17. Zhou T, Yan Y, Zhao C, et al. Resveratrol improves osteogenic differentiation of senescent bone mesenchymal stem cells through inhibiting endogenous reactive oxygen species production via AMPK activation. Redox Rep, 2019, 24(1): 62-69.
18. Moghanian A, Portillo-Lara R, Shirzaei Sani E, et al. Synthesis and characterization of osteoinductive visible light-activated adhesive composites with antimicrobial properties. J Tissue Eng Regen Med, 2020, 14(1): 66-81.
19. Chen LZ, Yao L, Jiao MM, et al. Novel resveratrol-based flavonol derivatives: Synthesis and anti-inflammatory activity in vitro and in vivo. Eur J Med Chem, 2019, 175: 114-128.
20. Parvez S, Karole A, Mudavath SL. Transport mechanism of hydroxy-propyl-beta-cyclodextrin modified solid lipid nanoparticles across human epithelial cells for the oral absorption of antileishmanial drugs. Biochim Biophys Acta Gen Subj, 2022, 1866(8): 130157. doi: 10.1016/j.bbagen.2022.130157.
21. Dai Z, Li Y, Quarles LD, et al. Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation. Phytomedicine, 2007, 14(12): 806-814.
22. Zhang W, Wang N, Yang M, et al. Periosteum and development of the tissue-engineered periosteum for guided bone regeneration. J Orthop Translat, 2022, 33: 41-54.
23. Wu ZL, Zhao J, Xu R. Recent advances in oral nano-antibiotics for bacterial infection therapy. Int J Nanomedicine, 2020, 15: 9587-9610.
24. Vishwakarma N, Jain A, Sharma R, et al. Lipid-based nanocarriers for lymphatic transportation. AAPS PharmSciTech, 2019, 20(2): 83. doi: 10.1208/s12249-019-1293-3.

Chinese Journal of Reparative and Reconstructive Surgery

Experimental study of resveratrol-solid lipid nanoparticles in promotion of osteogenic differentiation of bone marrow mesenchymal stem cells

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content