Abstract
Purpurogallin, a benzotropolone-containing natural compound, has been reported to exhibit numerous biological and pharmacological functions, such as antioxidant, anticancer, and anti-inflammatory effects. In this study, we enzymatically synthesized purpurogallin from pyrogallol and investigated its role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Purpurogallin attenuated the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts from bone marrow macrophages (BMMs) without causing cytotoxicity, and suppressed upregulation of osteoclast-specific markers, including TRAP (Acp5), cathepsin K (Ctsk), and dendritic cell-specific transmembrane protein (Dcstamp). However, purpurogallin did not affect the bone resorbing function of mature osteoclasts evident by the resorption pit assay. Activation of mitogen-activated protein kinases, Akt and IkB pathways in RANK signaling were not altered by purpurogallin, whereas the expression of c-Fos and NFATc1, key transcriptional regulators in osteoclastogenesis, was dramatically inhibited by purpurogallin. Purpurogallin also significantly reduced the expression level of B lymphocyte-induced maturation protein-1 (Blimp1) gene (Prdm1). Further, downregulation of Blimp1 led to forced expression of anti-osteoclastogenic genes, including interferon regulatory factor-8 (Irf8) and B-cell lymphoma 6 (Bcl6) genes. Taken together, our data suggested that purpurogallin inhibits osteoclast differentiation via downregulation of c-Fos and NFATc1.
Highlights
The interaction between bone-forming osteoblasts and bone-resorbing osteoclasts is crucial for maintaining bone homeostasis [1]
We investigated whether purpurogallin could inhibit receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation of bone marrow macrophages
To assess the effect of purpurogallin on RANKL-mediated osteoclast differentiation, bone marrow macrophages (BMMs) stimulated with M-CSF (10 ng/mL) and RANKL (20 ng/mL) were incubated in the presence or absence of 5 or 10 μM purpurogallin
Summary
The interaction between bone-forming osteoblasts and bone-resorbing osteoclasts is crucial for maintaining bone homeostasis [1]. Disruption of this homeostasis caused by a variety of pathophysiological conditions, such as hormonal perturbation, inflammation, aging, stress, and dietary habits, leads to skeletal diseases. An abnormal increase in osteoclast formation and activation results in bone loss associated with osteoporosis and osteolytic diseases [2]. Suppression of osteoclast differentiation or blocking osteoclast function can be an effective way for treating the skeletal diseases associated with abnormally enhanced activation of osteoclasts [3,4]. Natural compounds from medicinal plants and foods have drawn attention for developing more effective and safer therapeutic agents for skeletal diseases
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