The effects and mechanism of paeoniflorin in promoting osteogenic differentiation of MC3T3-E1

Abstract

Background The incidence of osteoporosis and osteoporotic fractures is increasing every year. Traditional Chinese Medicine (TCM) can shed new light on the treatment of osteoporosis. This study aimed to explore the role and mechanism of paeoniflorin in promoting osteogenic differentiation of an osteoblast precursor cell line (MC3T3-E1). Methods MC3T3-E1 cells were cultured in osteogenic induction medium (OIM) and OIM combined with different concentrations of paeoniflorin. The optimal dose of paeoniflorin was assessed by a cell counting kit-8 (CCK-8) assay. Then, alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining were performed to assess the osteogenic capacity of paeoniflorin. The transcription of osteogenic genes and the expression of osteogenic proteins were assessed by RT-PCR and Western blotting, respectively. The transcription of Wnt/β-catenin signaling pathway genes and proteins was assessed by RT-PCR and Western blotting, respectively. Finally, Dickkopf-1 (DKK-1), a Wnt/β-catenin signaling pathway inhibitor, was used to identify whether the Wnt/β-catenin signaling pathway was involved in the osteogenic differentiation of paeoniflorin. Osteoclastogenesis in RAW264.7 cells was identified by tartrate-resistant acid phosphatase (TRAP) staining. Results At concentrations ranging from 0.1 to 100 μM, paeoniflorin was not cytotoxic to MC3T3-E1 cells. Paeoniflorin significantly increased the osteogenic differentiation of MC3T3-E1 cells in a dose-dependent manner. Moreover, paeoniflorin significantly increased osteogenic differentiation gene and protein expression. Through bioinformatic analysis, paeoniflorin-affected genes were found to be involved in different signaling pathways, such as the Wnt/β-catenin signaling pathway. Paeoniflorin enhanced β-catenin and CyclinD1 expression compared with that of the control groups. DKK-1 partially reversed the promoting effects of paeoniflorin in promoting osteogenic differentiation of MC3T3-E1 cells. Moreover, paeoniflorin inhibited the osteoclastogenesis of RAW264.7 cells. Conclusion Paeoniflorin promotes osteogenic differentiation in MC3T3-E1 cells by regulating the Wnt/β-catenin pathway. Paeoniflorin is a potential therapeutic agent for the treatment of osteoporosis.

Gujin Dan is a Chinese medicine formulation that stimulates cell proliferation and differentiation by controlling multiple genes involved in MC3T3-E1 cells

“…Radix Paeoniae Alba containing Paeoni orin has been widely used in the treatment of osteoporosis. Paeoni orin treatment of osteoporosis can be divided into two general directions: inhibiting osteoclast activity [70] and improving osteoblast activity [71,72], It slows bone resorption by inhibiting osteoclast activity and promotes bone formation by increasing osteoblast activity. Corydalis Yanhusuo contains Tetrahydropalmatine, Experimental studies in vivo and in vitro have shown that Tetrahydropalmatine inhibits osteoclast formation by inhibiting NF-κB and MAPK pathways [73].…”

Protective Effect and Mechanism of Plant-Based Monoterpenoids in Non-alcoholic Fatty Liver Diseases

“…In early 1998, the U.S. Food and Drug Administration (FDA) approved the sale of paeoniflorin. 66 Paeoniflorin has attracted much attention worldwide owing to its multiple positive effects on alleviating liver diseases, including cholestasis, liver fibrosis, hepatocellular carcinoma, and NAFLD. 67 In a NAFLD animal model, Zhang et al 68 first examined these pharmacological effects in HFD-fed male C57BL/6J mice from a comprehensive perspective.…”

“…Paeoniflorin, a kind of white powder mainly derived from the root of the Chinese herb Paeonia lactiflora, is a water-soluble pinane monoterpenoid with a cage-like pinnae skeleton. In early 1998, the U.S. Food and Drug Administration (FDA) approved the sale of paeoniflorin . Paeoniflorin has attracted much attention worldwide owing to its multiple positive effects on alleviating liver diseases, including cholestasis, liver fibrosis, hepatocellular carcinoma, and NAFLD .…”

Sword Bean (Canavalia gladiata) Pods Induce Differentiation in MC3T3-E1 Osteoblast Cells by Activating the BMP2/SMAD/RUNX2 Pathway

“…Similarly, Dendropanax morbifera increased downstream ALP, OPN, OCN, and RUNX2 via BMP2/p38 MAPK/JNK and SMAD1/5/9 signaling pathways [17]. In addition, Panax ginseng [18] and paeoniflorin [19] have also been shown to promote osteoblast differentiation and bone formation.…”