Angelica sinensis polysaccharide promotes the proliferation and osteogenic differentiation of human dental pulp stem cells (hDPSCs) by activating the wnt/β-catenin pathway

Main Article Content

Tiantian Mao
Youjian Peng
Ruobing Peng
Xiaoying Wei


Angelica polysaccharide, human dental pulp stem cells, osteogenic differentiation, proliferation, Wnt/β-catenin pathway


Human dental pulp stem cells (hDPSCs) are capable of forming mineralized nodules. The proliferation and osteogenic differentiation of hDPSCs are very important for alleviating tooth defects caused by related diseases. Angelica polysaccharide (ASP) is the main bioactive ingredient extracted from the angelica root. ASP has a variety of biological functions, including immune regulation, antitumor activity, and hematopoiesis. However, its possible effects on hDPSCs are still unclear. In this study, we aimed to investigate the role of ASP in periodontal diseases. We found that ASP promoted the proliferation of hDPSCs and osteogenic differentiation of hDPSCs. We further found that it promoted the expression of osteogenic-related genes, including ALP, RUNX2, Col1a1, and OCN. Mechanically, we found that ASP activated the Wnt/β-catenin pathway. In conclusion, our results suggested that ASP promoted the proliferation and osteogenic differentiation of hDPSCs via the Wnt/β-catenin pathway.

Abstract 232 | PDF Downloads 103 HTML Downloads 57 XML Downloads 52


Ali, M.Y., Jannat, S., Jung, H.A. and Choi, J.S., 2021. Insulin-mimetic dihydroxanthyletin-type coumarins from angelica decursiva with protein tyrosine phosphatase 1B and alpha-glucosidase inhibitory activities and docking studies of their molecular mechanisms. Antioxidants (Basel) 10(2). 10.3390/antiox10020292

Chang, J., Li, Y., Wang, X., Hu, S., Wang, H., Shi, Q., et al. 2017. Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/beta-catenin pathway in vitro and in vivo. Sci Rep 7(1): 7605. 10.1038/s41598-017-07194-9

Chao, Y.H., Yang, W.T., Li, M.C., Yang, F.L. and Lee, R.P., 2021. Angelica dahurica and rheum officinale facilitated diabetic wound healing by elevating vascular endothelial growth factor. Am J Chin Med 49(6): 1515–1533. 10.1142/S0192415X21500713

Cheng, C.Y., Huang, H.C., Kao, S.T. and Lee, Y.C., 2021. Angelica sinensis extract promotes neuronal survival by enhancing p38 MAPK-mediated hippocampal neurogenesis and dendritic growth in the chronic phase of transient global cerebral ischemia in rats. J Ethnopharmacol 278: 114301. 10.1016/j.jep.2021.114301

Guo, Y.R., Jin, H., Kim, M., Shin, M.B., Lee, J.H., Maeng, S., et al. 2021. Synergistic neuroprotective effects of mature silkworm and angelica gigas against scopolamine-induced mild cognitive impairment in mice and H2O2-induced cell death in HT22 mouse hippocampal neuronal cells. J Med Food 24(5): 505–516. 10.1089/jmf.2020.4839

He, Y., Zhong, Y., Bao, Z., Wang, W., Xu, X., Gai, Y., et al. 2021 Evaluation of angelica decursiva reference genes under various stimuli for RT-qPCR data normalization. Sci Rep 11(1): 18993. 10.1038/s41598-021-98434-6

Huang, W.Y., Youk, J.S., Han, B.K., Heo, W., Yun, B.S., Kim, J.S.,et al. 2011. Improvement of fatigue symptoms and endurance capacity by the combined administration of Cervus elaphus L., Angelica gigas Nakai, and Astragalus membranaceus Bunge. J Med Food 24(6): 577–585. 10.1089/jmf.2020.4743

Kwon, D.A., Kim, Y.S., Kim, S.K., Baek, S.H., Kim, H.K. and Lee, H.S., 2021. Antioxidant and antifatigue effect of a standardized fraction (HemoHIM) from Angelica gigas, Cnidium officinale, and Paeonia lactiflora. Pharm Biol 59(1): 391–400. 10.1080/13880209.2021.1900878

Li, C., Liu, S., Zheng, J. and Xue, Y., 2021. Angelica sinensis polysaccharide (ASP) attenuates diosbulbin-B (DB)-induced hepatotoxicity through activating the MEK/ERK pathway. Bioengineered 12(1): 3516–3524. 10.1080/21655979.2021.1950280

Liu, S., Wang, Y.N., Ma, B., Shao, J., Liu, H. and Ge, S., 2021. Gingipain-responsive thermosensitive hydrogel loaded with SDF-1 facilitates in situ periodontal tissue regeneration. ACS Appl Mater Interfaces 13(31): 36880–36893. 10.1021/acsami.1c08855

Liu, Y., Fang, J., Zhang, Q., Zhang, X., Cao, Y., Chen, W., et al., 2020. Wnt10b-overexpressing umbilical cord mesenchymal stem cells promote critical size rat calvarial defect healing by enhanced osteogenesis and VEGF-mediated angiogenesis. J Orthop Translat 23: 29–37. 10.1016/

Luan, Y., Luan, Y., Feng, Q., Chen, X., Ren, K.-D. and Yang, Y., 2021a. Emerging role of mitophagy in the heart: therapeutic potentials to modulate mitophagy in cardiac diseases. Oxidative Medicine and Cellular Longevity 2021: 13. 10.1155/2021/3259963

Luan, Y., Luan, Y., Yuan, R.X., Feng, Q., Chen, X. and Yang, Y., 2021b. Structure and function of mitochondria-associated endoplasmic reticulum membranes (MAMs) and their role in cardiovascular diseases. Oxid Med Cell Longev 2021: 4578809. 10.1155/2021/4578809

Nai, J., Zhang, C., Shao, H., Li, B., Li, H., Gao, L., et al. 2021. Extraction, structure, pharmacological activities and drug carrier applications of Angelica sinensis polysaccharide. Int J Biol Macromol 183: 2337–2353. 10.1016/j.ijbiomac.2021.05.213

Song, X., Kong, J., Song, J., Pan, R. and Wang, L., 2021. Angelica sinensis polysaccharide alleviates myocardial fibrosis and oxidative stress in the heart of hypertensive rats. Comput Math Methods Med 2021: 6710006. 10.1155/2021/6710006

Su, G., Yan, Z. and Deng, M., 2020. Sevoflurane inhibits proliferation, invasion, but enhances apoptosis of lung cancer cells by Wnt/beta-catenin signaling via regulating lncRNA PCAT6/miR-326 axis. Open Life Sci 15: 159–172. 10.1515/biol-2020-0017

Tsuruda, M., Morino-Koga, S., Ogawa, Minetar., 2021. Bone morphogenetic protein 4 differently promotes distinct VE-cadherin precursor stages during the definitive hematopoietic development from embryonic stem cell-derived mesodermal cells. Exp Hematol. 10.1016/j.exphem.2021.08.008.

Wang, K., Song, Z., Wang, H., Li, Q., Cui, Z. and Zhang, Y., 2016. Angelica sinensis polysaccharide attenuates concanavalin A-induced liver injury in mice. Int Immunopharmacol 31: 140–148. 10.1016/j.intimp.2015.12.021

Yang, Y., Yang, L., Wu, Y. and Yuan, J., 2021a. [Dexmedetomidine-mediated Wnt pathway inhibits sevoflurane-induced cognitive impairment in neonatal rats]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 43(2): 235–246. 10.3881/j.issn.1000-503X.12913

Yang, Y., Yang, L., Yuan R.-X. and Luan, Y., 2021b. Histone methylation related therapeutic challenge in cardiovascular diseases. Frontiers in Cardiovascular Medicine 8:710053. 10.3389/fcvm.2021.710053

Yang, Z., Liu, J., Fu, J., Li, S., Chai, Z. and Sun, Y., 2021c. Associations between WNT signaling pathway-related gene polymorphisms and risks of osteoporosis development in Chinese postmenopausal women: a case-control study. Climacteric 1–7. 10.1080/13697137.2021.1941848

Zhang, H., Li, X., Li, J., Zhong, L. and Chen, X., 2021. Chen S. SDF-1 mediates mesenchymal stem cell recruitment and migration via the SDF-1/CXCR4 axis in bone defect. J Bone Miner Metab 39(2): 126–138. 10.1007/s00774-020-01122-0

Zhou, J., Gao, Y.H., Zhu, B.Y., He, W.F., Wang, G., Xian, C.J., et al. 2021. The frequency window effect of sinusoidal electromagnetic fields in promoting osteogenic differentiation and bone formation involves extension of osteoblastic primary cilia and activation of protein kinase A. Cell Biol Int. 45: 1685–1697. 10.1002/cbin.11606

Zhou, J., Gao, Y.H., Zhu, B.Y., Shao, J.L., Ma, H.P., Xian, C.J., et al. 2019. Sinusoidal electromagnetic fields increase peak bone mass in rats by activating Wnt10b/beta-Catenin in primary cilia of osteoblasts. J Bone Miner Res 34(7): 1336–1351. 10.1002/jbmr.3704

Zhu, H., You, J., Wen, Y., Jia, L., Gao, F., Ganesan, K. and Chen, J., 2021. Tumorigenic risk of Angelica sinensis on ER-positive breast cancer growth through ER-induced stemness in vitro and in vivo. J Ethnopharmacol 280: 114415. 10.1016/j.jep.2021.114415