Psoralen stimulates osteoblast proliferation through the activation of nuclear factor-κB-mitogen-activated protein kinase signaling

Abstract

Abstract. Osteoporosis is a systemic skeletal disease that leads to increased bone fragility and susceptibility to fracture. Approximately 50% of postmenopausal women develop osteoporosis as a result of postmenopausal estrogen deficiency. To reduce fractures related to osteoporosis in women, previous studies have focused on therapeutic strategies that aim to increase bone formation or decrease bone resorption. However, pharmacological agents that aim to improve bone fracture susceptibility exhibit side effects. Current studies are investigating natural alternatives that possess the benefits of selective estrogen receptor modulators (SERMs) without the adverse effects. Recent studies have indicated that phytoestrogen may be an ideal natural SERM for the treatment of osteoporosis. In Chinese herbal medicine, psoralen, as the predominant substance of Psoralea corylifolia, is considered to be a phytoestrogen and is used as a remedy for osteoporosis. A number of studies have demonstrated the efficacy of psoralen in bone formation. However, the pathways and underlying molecular mechanisms that participate in psoralen-induced osteoblast formation are not well understood. In the present study, hFOB1.19 cells were treated with psoralen at different concentrations (0, 5, 10, 15 and 20 µM) for 0, 24, 36, 48 and 72 h, respectively. Reverse transcription-quantitative polymerase chain reaction and western blot assays were performed to detect glucose transporter 3 (GLUT3) expression. A cell counting kit-8 assay was used to analyze cell proliferation. In addition the effects of mitogen activated protein kinase inhibitors on extracellular signal-regulated kinase (ERK), phosphorylated (p)-ERK, p38, p-p38, c-Jun N-terminal kinase (JNK) and p-JNK expressions and cell proliferation were measured, as was the effect of nuclear factor (NF)-κB inhibitor on P65 and GLUT3 expressions and cell proliferation. The results indicated that psoralen stimulates hFOB1.19 cell proliferation in a dose-dependent manner (P<0.05). Phospho-ERK, p38 and JNK were markedly increased by psoralen compared with the control group (P<0.05), and the specific inhibitors of ERK (SCH772984), p38 (SB203580) and JNK (SP600125) reversed the stimulatory effects of psoralen on signal marker phosphorylation (P<0.05). The rate of psoralen-induced cell proliferation was significantly suppressed by inhibitors of ERK, JNK and p38 compared with psoralen treatment alone (P<0.05). In addition, psoralen stimulated osteoblast proliferation via the NF-κB signaling pathway. Therefore, the present findings suggest that psoralen may be a potential natural alternative to SERMs in the treatment of osteoporosis and fractures.

Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts

“…Psoralen is extracted from the fruits of Psoralea corylifolia L . It has been reported to have antioxidant, antibacterial, antidepressant, antitumor, antidiabetic, and estrogen‐like activities (24, 25). Previous studies have demonstrated that psoralen inhibits metastasis of breast cancer to bone in vivo and promotes the formation of new bone mixed with collagen matrix in vivo (26, 27).…”

A Review of the Pharmacological Properties of Psoralen

“…However, the effect of psoralen on the phosphorylation of ASK1, JNK, and MAPK P38 in osteoblasts and osteoclasts remains controversial and requires further study (Li F. et al, 2017;Chen et al, 2017a;Chai et al, 2018;Zhang et al, 2019).…”

“…Alkaline phosphatase (ALP) is a calcium-binding transporter located in the cell membrane which promotes cell maturation and calcification. Studies have demonstrated that psoralen increases the gene expression levels of osteoblast-specific markers such as GLUT3, Runx2, Col-I, osteocalcin, bone sialoprotein, and osterix, in addition to enhancing the activity of ALP, increasing colony formation in fibroblasts and promoting osteoblast differentiation ( Tang et al, 2011 ; Yang et al, 2012 ; Li F. et al, 2017 ; Zhang et al, 2019 ).…”

Protective Effects of Selected Botanical Agents on Bone

“…Bakuchiol has a three-fold higher binding affinity for estrogen receptor alpha (ERα) than for estrogen receptor beta (ERβ) [ 13 , 27 ]. It does not have significant uterotrophic activity, although demonstrating in vitro estrogenic activity [ 27 , 45 ]. It can reduce postmenopausal bone loss by increasing ALP, calcium concentrations, serum estrogen concentration, and bone mineral density [ 27 , 45 ].…”

“…It does not have significant uterotrophic activity, although demonstrating in vitro estrogenic activity [ 27 , 45 ]. It can reduce postmenopausal bone loss by increasing ALP, calcium concentrations, serum estrogen concentration, and bone mineral density [ 27 , 45 ]. Psoralen, a coumarin-like derivative extracted from the fruit of P. corylifolia L., has stimulatory effects on new bone formation [ 27 , 46 , 47 ].…”