Schisandrin B regulates MC3T3-E1 subclone 14 cells proliferation and differentiation through BMP2-SMADs-RUNX2-SP7 signaling axis

Abstract

Schisandrin B (SchB) is the highest content of biphenyl cyclooctene lignans in Schisandra chinensis. It has been reported to have a variety of pharmacological effects, including anti-inflammatory, anti-oxidant, anti-cancer, heart protection, liver protection. In this study, we found that SchB can promote the proliferation of MC3T3-E1 subclone 14 cells. Meanwhile, we found that SchB can regulate the BMP2-SMADs signaling pathway by increasing gene and protein expression of those relative biomolecules. Furthermore, SchB can raise the RUNX2 and SP7 expression in both mRNA and protein levels. Since the role of BMP2-SMADs-RUNX2-SP7 signaling axis in osteoblast proliferation and differentiation has been well documented. The present experimental findings indicate that SchB could promote the proliferation and differentiation of osteoblasts through BMP2-SMADs-RUNX2-SP7 signaling axis. Schisandrin B (SchB) is one of the lignans with high content from Schisandra chinensis 1. SchB has been reported to have a variety of pharmacological activities, including anti-inflammation 2 , antioxidation 3 , anti-cancer 4,5 etc. It is worth noting that SchB has been reported to ameliorate chondrocytes inflammation and osteoarthritis by inhibiting NF-κB and MAPK signaling pathways 6. These findings suggest that SchB may play a potential role in alleviate bone disease. However, the effect of SchB on osteoblasts is unknown. MC3T3-E1 subclone 14 cells are often used to study the proliferation and differentiation of osteoblasts 7-9. It is well known BMP2-SMADs signaling pathway play a key role in mediating osteoblast differentiation and osteogenesis 10. While Runx2 and SP7 are transcription factors that are essential for osteoblast proliferation and differentiation 11,12. Here, the effects of SchB on the proliferation of MC3T3-E1 subclone 14 cells were evaluated by MTT assay, and the effects of SchB on the expression of genes and proteins related to BMP2-SMADs-RUNX2-SP7 signaling axis were investigated by quantitative PCR and western blot, respectively. Results SchB promotes MC3T3-E1 subclone 14 cells proliferation in a certain concentration range. Osteoblasts are responsible for bone synthesis, remodeling and healing 13. Osteoblast proliferation plays an important role in bone maintenance and development. In the present study, SchB stimulated the proliferation of MC3T3-E1 subclone 14 cells in gradually increase degrees at the concentration of 1.25-40 μM, while showed cytotoxicity at concentrations of 80 μM and 100 μM. In addition, after 24 h of treatment, the effect of SchB on the proliferation of MC3T3-E1 cells tended to be flat, and the intensity of action did not increase significantly with the extension of time (Fig. 1).

Anti-Cancer Effects of α-Cubebenoate Derived from Schisandra chinensis in CT26 Colon Cancer Cells

“…The anti-cancer activity of α-cubebenoate isolated from S. chinensis fruit was determined as previously described for gomisin J [ 25 ]. Additionally, α-cubebenoate used in this assay was decided based on the results of previous studies on the anti-obesity activity of α-cubebenoate and the anti-cancer activity of gomisin A [ 13 , 23 ]. Briefly, the two cell types were evenly seeded at a density of 7 × 10 3 cells/200 μL in RPMI 1640 and grown in a 5% CO 2 incubator for 24 h at 37°C.…”

“…The anti-cancer activities of schisantherins A, B, and C, gomisins A, B, and N, deoxyschisandrin, and α-iso-cubebenol derived from S. chinensis have been shown to induce apoptosis, suppress cell cycle arrest, and inhibit the proliferations of various cancer cells, including those of breast, colon, and ovarian cancer and hepatic carcinoma [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. However, other compounds present in S. chinensis including α-cubebenoate, cubebene, gomisin C, D, E, F, G, K3, and J have not been evaluated for anti-cancer activity in mammalian cells.…”

BMP Signaling Pathway in Dentin Development and Diseases

“…Conditional Smad4 KO mice (Dmp1-Cre;Smad4fx/fx) led to dentin defects, with wide predentin, thin dentin, disorganized dentin tubules, and decreased expression of Bsp, Collα1, Dmp1, and Dspp genes exhibited [ 156 ]. Canonical Smad signaling enhanced dental mesenchymal cell differentiation and Dspp expression via the action of Dlx5, Msx2, Osx, Runx2, Smads, and other compounds [ 92 , 157 , 158 , 159 , 160 ].…”

Cardioprotective Potential of Berries of Schisandra chinensis Turcz. (Baill.), Their Components and Food Products

“…Various in vitro and in vivo studies have found them to demonstrate various antioxidative, anti-inflammatory, anticancer, and antiviral properties, among others. For example, S. chinensis has an inhibitory effect on cytochrome P450, family 3, subfamily A (CYP3A), and P-glycoprotein (P-gp), which can mediate metabolism or efflux of substrates, and may interact with many drugs [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. In addition, Nasser et al [ 9 ] described various biological properties of schisandrin B.…”