Bergapten promotes bone marrow stromal cell differentiation into osteoblasts in vitro and in vivo

Abstract

Many recent studies have suggested that bergapten (BP), a class of native compound with numerous biological activities such as anti-resorptive properties, may exert protective effects against postmenopausal bone loss. However, it remains unknown whether BP regulates or improves the osteogenic function of bone marrow stromal cells (BMSCs) in the treatment and prevention of osteoporosis. In our study, BMSCs were cultured in osteogenic induction medium with the addition of BP for 2 weeks and an ovariectomized mouse model of osteoporosis was used to investigate the anti-resorptive effect of BP by gavage administration for 3 months. The concentrations of BP used were 0.1, 1, and 10 μmol/L in vitro and the gavage dose was 20 mg/kg/d. The result of our study indicated that BP promotes the expression of alkaline phosphatase (ALP) by BMSCs in vitro in a dose-dependent manner, as revealed by ALP staining. Runt-related transcription factor 2 and osteocalcin were up-regulated both in vitro and vivo, while osterix and collagen Iα1, assessed by immunofluorescence and immunohistochemistry, were correspondingly raised in the presence of BP in BMSCs in vitro. In addition, a protective effect of BP against ovariectomy-induced bone loss was found by distal femur micro-CT scanning, with improvements of bone metabolism parameters such as bone mineral density, trabecular number, and trabecular separation. Furthermore, WNT/β-catenin signaling was activated in the presence of BP in BMSCs in osteogenic culture. Finally, BP promoted differentiation of BMSCs into osteoblasts by up-regulation of the WNT/β-catenin pathway.

Glucocorticoids decreased Cx43 expression in osteonecrosis of femoral head: The effect on proliferation and osteogenic differentiation of rat BMSCs

“…The results showed that Cx43 expression was decreased significantly in the model group in a comparison with the control group, and also the expressions of Runx2, ALP and COLⅠ were decreased significantly in the model group. All these factors are known as the primary regulators or associated factors of the osteogenic differentiation process 43,44 . Osteocytes are mainly originated from BMSCs, where BMSCs firstly undergo lineage differentiation and become pre‐osteoblasts.…”

“…All these factors are known as the primary regulators or associated factors of the osteogenic differentiation process. 43,44 Osteocytes are mainly originated from BMSCs, where BMSCs firstly undergo lineage differentiation and become pre-osteoblasts. Glucocorticoid use could inhibit the differentiation and maturation of pre-osteoblasts through inhibiting Runx2 expression, which followed by a decrease of the expressions of ALP and COLⅠ.…”

Botanical Sources, Chemistry, Analysis, and Biological Activity of Furanocoumarins of Pharmaceutical Interest

“…The central role fulfilled by BMP-2 in the activity of furanocoumarins was evident also in young rats treated for 7 consecutive days with bergapten, where it was possible to note a remarkable increase in the bone volume, phosphorylation of SMAD 1/5/8, p38, and ERK, and BMP-2 expression at the level of the tibia. Bergapten modulation of key enzymes in bone health promotion is not limited to the above described proteins, but it involves also the expression of Runt-related transcription factor 2 (RUNX2), modulation of the Wnt/β-catenin pathway, and osteocalcin (noncollagenous protein secreted by osteoblasts) [146,147,148]. Oral administration of bergapten for 3 months to an ovariectomized mouse model (one of the main animal models for studying postmenopausal osteoporosis) resulted in a remarkable decrease in delaying bone loss as shown by analysis of the bone mineral density, separation, and number of trabeculas.…”

Dietary Coumarins

“…Earlier, this compound was shown to inhibit diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK, and NF-κB signaling pathways in osteoprotegerin knockout mice and thus to protect trabecular structure and decrease osteoclastogenic differentiation (Li et al 2016b). This coumarin could also promote bone marrow stromal cell differentiation into osteoblasts in vitro and in vivo using a mouse model (Xiao et al 2015). The protective effect of 27 against ovariectomy-induced bone loss was found by distal femur micro-CT scanning, with improvements of bone metabolism parameters such as bone mineral density, trabecular number, and trabecular separation.…”