Fucoidan promotes osteoblast differentiation via JNK- and ERK-dependent BMP2–Smad 1/5/8 signaling in human mesenchymal stem cells

Abstract

Fucoidan has attracted attention as a potential drug because of its biological activities, which include osteogenesis. However, the molecular mechanisms involved in the osteogenic activity of fucoidan in human alveolar bone marrow-derived mesenchymal stem cells (hABM-MSCs) remain largely unknown. We investigated the action of fucoidan on osteoblast differentiation in hABM-MSCs and its impact on signaling pathways. Its effect on proliferation was determined using the crystal violet staining assay. Osteoblast differentiation was evaluated based on alkaline phosphatase (ALP) activity and the mRNA expression of multiple osteoblast markers. Calcium accumulation was determined by Alizarin red S staining. We found that fucoidan induced hABM-MSC proliferation. It also significantly increased ALP activity, calcium accumulation and the expression of osteoblast-specific genes, such as ALP, runt-related transcription factor 2, type I collagen-α 1 and osteocalcin. Moreover, fucoidan induced the expression of bone morphogenetic protein 2 (BMP2) and stimulated the activation of extracellular signal-related kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase by increasing phosphorylation. However, the effect of fucoidan on osteogenic differentiation was inhibited by specific inhibitors of ERK (PD98059) and JNK (SP600125) but not p38 (SB203580). Fucoidan enhanced BMP2 expression and Smad 1/5/8, ERK and JNK phosphorylation. Moreover, the effect of fucoidan on osteoblast differentiation was diminished by BMP2 knockdown. These results indicate that fucoidan induces osteoblast differentiation through BMP2–Smad 1/5/8 signaling by activating ERK and JNK, elucidating the molecular basis of the osteogenic effects of fucoidan in hABM-MSCs.

TGF-β3 and IGF-1 synergy ameliorates nucleus pulposus mesenchymal stem cell differentiation towards the nucleus pulposus cell type through MAPK/ERK signaling

“…On the other hand, TGF/Smad signaling also plays an essential role in both the chondrocyte-like cell differentiation and cartilaginous tissue development (Li et al, 2005;van der Kraan et al, 2009). Several studies proposed the crosstalk between MAPK/ERK and TGF/Smad signaling, and the activation of non-canonical TGF-b signaling by ERK (Boye et al, 2015;Kim et al, 2015;Liu et al, 2014;Ottley & Gold, 2014). In this study, the phosphorylation of Smad3 partly decreased by U0126 in condition of TGF-b3 only or combined with IGF-1, and totally inhibited in IGF-1 treatment.…”

Triptolide inhibits the function of TNF-α in osteoblast differentiation by inhibiting the NF-κB signaling pathway

“…It has been reported that osteoblast differentiation is induced by c-Jun N-terminal kinase and extracellular signal-related kinase-dependent BMP2-Smad 1/5/8 signaling in human mesenchymal stem cells (32). Cytokines such as TNF-α have a dual action in bone formation and are important in various skeletal diseases, including rheumatoid arthritis, inflammation and osteolysis (33).…”

The mechanism of a chitosan-collagen composite film used as biomaterial support for MC3T3-E1 cell differentiation

“…Multiple signals, such as growth/hormone factor stimulation and matrix-integrin binding, activate the Erk pathway in bone. Activated Erk promotes calvarial osteoblast differentiation through the downstream transcription factor Runx2 at Ser 301 and Ser 319 residues, and the mRNA levels of specific osteoblast differentiation-related marker genes are increased123456.…”