Purslane Suppresses Osteoclast Differentiation and Bone Resorbing Activity via Inhibition of Akt/GSK3β-c-Fos-NFATc1 Signaling in Vitro and Prevents Lipopolysaccharide-Induced Bone Loss in Vivo

• Published in: Biological & pharmaceutical bulletin 2015/01/01, Vol.38(1), pp.66-74
• Main Authors: Kim, Ju-Young, Oh, Hyun Mee, Kwak, Sung Chul, Cheon, Yoon-Hee, Lee, Myeung Su, Rho, Mun Chual, Oh, Jaemin
• Format: Article
• Language: English
• Subjects: Animals; bone loss; Bone Marrow Cells - cytology; Bone Resorption - chemically induced; Bone Resorption - metabolism; Bone Resorption - prevention & control; Cell Differentiation - drug effects; Glycogen Synthase Kinase 3 - antagonists & inhibitors; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Lipopolysaccharides; Male; Mice, Inbred ICR; natural medicine; NFATC Transcription Factors - antagonists & inhibitors; NFATC Transcription Factors - metabolism; osteoclast; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - metabolism; osteoporosis; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Portulaca; Portulaca oleracea; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-fos - antagonists & inhibitors; Proto-Oncogene Proteins c-fos - metabolism; purslane (Portulaca oleracea); RANK Ligand - pharmacology; Signal Transduction - drug effects
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b14-00567

Purslane (Portulaca oleracea L.) is popular as a potherb in many areas of Europe, Asia, and the Mediterranean region and is widely distributed around the globe. It has a wide range of pharmacological effects, such as antibacterial, anti-aging, anti-inflammatory, and anti-oxidative properties. Although the extract of purslane has numerous beneficial pharmacological effects, its effect on osteoclasts remains unknown. We aimed to investigate the anti-osteoclastogenic activity in vitro and in vivo and to elucidate the underlying mechanism. The effect of purslane on the differentiation and function of bone marrow-derived macrophages (BMMs) into osteoclasts was examined using a phenotype assay such as tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining, and pit assay and followed by confirmation by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. To address the effect of purslane in vivo, the inflammatory, lipopolysaccharide (LPS)-induced osteolysis mouse model was chosen. Bone volume and bone microarchitecture were evaluated by microcomputed tomography and histologic analysis. Purslane inhibited receptor activator of nuclear factor-kappa B ligand (RANKL)-stimulated osteoclast differentiation accompanied by inhibition of Akt/glycogen synthase kinase 3β (GSK3β) signaling, which could underlie purslane-induced downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1) expression levels, transcription factors that regulate osteoclast-specific genes, as well as osteoclast fusion and resorption-related molecules. Moreover, in vivo studies further verified the bone protection activity of purslane in the LPS-induced osteolysis animal model. Purslane could exhibit its anti-osteoclastogenic activity by inhibiting Akt/GSK3β-c-Fos-NFATc1 signaling cascades. Therefore, purslane is a potential natural medicine for the treatment of osteoclast-related diseases.