Piceatannol attenuates RANKL-induced osteoclast differentiation and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promotes Caspase3-mediated apoptosis of mature osteoclasts

Abstract

Osteoclasts are multinuclear giant cells that have unique ability to degrade bone. The search for new medicines that modulate the formation and function of osteoclasts is a potential approach for treating osteoclast-related bone diseases. Piceatannol (PIC) is a natural organic polyphenolic stilbene compound found in diverse plants with a strong antioxidant and anti-inflammatory effect. However, the effect of PIC on bone health has not been scrutinized systematically. In this study, we used RAW264.7, an osteoclast lineage of cells of murine macrophages, to investigate the effects and the underlying mechanisms of PIC on osteoclasts. Here, we demonstrated that PIC treatment ranging from 0 to 40 µM strongly inhibited osteoclast formation and bone resorption in a dose-dependent manner. Furthermore, the inhibitory effect of PIC was accompanied by the decrease of osteoclast-specific genes. At the molecular level, PIC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK1/2), NF-κB p65, IκBα and AKT. Besides, PIC promoted the apoptosis of mature osteoclasts by inducing caspase-3 expression. In conclusion, our results suggested that PIC inhibited RANKL-induced osteoclastogenesis and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promoted caspase3-mediated apoptosis of mature osteoclasts, which might contribute to the treatment of bone diseases characterized by excessive bone resorption.

Inhibitory Effect of a Rosmarinic Acid-Enriched Fraction Prepared from Nga-Mon (Perilla frutescens) Seed Meal on Osteoclastogenesis through the RANK Signaling Pathway

“…Moreover, oxidative stress and proinflammatory cytokines can activate the differentiation of osteoclasts and osteoporosis. Many investigators reported that abundantly polyphenolic antioxidants such as genistein, quercitrin, ferulic acid, piceatannol, and taxifolin can inhibit the degradation of the bone matrix in osteoclasts, and induce alkaline phosphatase activity and matrix protein synthesis in osteoblasts [ 44 , 63 , 64 , 65 , 66 ]. Plants are the main sources of phytochemicals, antioxidants, and anti-inflammatory agents [ 3 , 30 ].…”

Osteoclastic effects of mBMMSCs under compressive pressure during orthodontic tooth movement

“…RANKL, a member of the tumour necrosis factor superfamily, plays an important role in osteoclastic differentiation [38]. It has been shown that RAW264.7 osteoclast precursor cells directly differentiate into osteoclasts in response to RANKL alone [39][40][41][42]. RANKL interacts with RANK to activate the downstream signalling molecule nuclear factor κB (NF-κB), which regulates expression of various osteoclast genes, such as MMP-9 and TRAP [43][44][45][46][47].…”

<p>Piceatannol Suppresses the Proliferation and Induced Apoptosis of Osteosarcoma Cells Through PI3K/AKT/mTOR Pathway</p>

“…18,19 Recently, the anti-tumor activity of PIC has gradually attracted the attention of clinical workers, and there are some scholars have reported that PIC could inhibit the invasion, migration and adhesion of breast cancer cells by blocking the activation of PI3K/AKT and NF-κB pathway. 20 In the orthopedic system, Yan et al 21 pointed out that PIC not only suppressed bone resorption and osteoclastogenesis but also accelerated apoptosis of mature osteoclasts, which might be beneficial to the therapy of correlative bone diseases. In a cell study, Wolter et al 22 treated human colorectal cancer cell lines with PIC, and found that the drug reduced cell proliferation rate and inhibited cell cycle progression at S phase, in a time-and concentration-dependent manner.…”