N‐(3‐methoxybenzyl)‐(9Z,12Z,15Z)‐octadecatrienamide promotes bone formation via the canonical Wnt/β‐catenin signaling pathway

Abstract

Osteoporosis is characterized by low bone mineral density and microarchitectural deterioration of bone tissue. N-(3-methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide (MBOC) is one of the macamides isolated from Maca (Lepidium meyenii Walp.), a cruciferous plant from the Andes of Peru. In this study, C3H/10T1/2 mesenchymal stem cells were treated with MBOC in osteogenic induction medium. An ovariectomized (OVX) mouse model was used to investigate the effect of 1-month MBOC treatment on the prevention of postmenopausal osteoporosis. Remarkably, trabecular thickness, trabecular number, and bone volume/tissue volume of the distal femoral metaphysis were significantly increased in OVX + MBOC mice compared with OVX mice, as revealed by microcomputed tomography analysis. Trabecular separation was decreased in OVX + MBOC mice compared with OVX mice. Consistently, MBOC increased the levels of osteocalcin and runt-related transcription factor 2 in OVX mice, as well as the expression of runt-related transcription factor 2, osterix, and alkaline phosphatase in C3H/10T1/2 cells. Mechanistically, MBOC activates the canonical Wnt/β-catenin signaling pathway via inhibiting phosphorylation of GSK-3β at Tyr216 and maintaining β-catenin expression. Collectively, the current study demonstrates the robustness of MBOC in the induction of mesenchymal stem cells osteogenic differentiation and consequent bone formation, suggesting that MBOC may be a potentially effective drug to treat postmenopausal osteoporosis. KEYWORDS bone metabolism, Maca, N-(3-methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide, postmenopausal osteoporosis, Wnt/β-catenin

Citrate-Stabilized Gold Nanorods-Directed Osteogenic Differentiation of Multiple Cells

“…Upon Wnt activation, GSK-3β was inhibited via phosphorylation of Ser9, causing the accumulation of β-catenin in the cytoplasm, thus improving the expression of Runx2. 40 Therefore, potential molecular mechanisms were investigated by examining the expression of key markers, such as β-catenin and p-GSK-3β, which might be involved in the relevant signaling pathways during the osteogenic differentiation of MC3T3-E1 cells. 41,42 As expected, WB analysis demonstrated that the level of β-catenin and p-GSK-3β was increased in Cit-NRIII-treated cells (Figure 5I-K), indicating that the Wnt/β-catenin signaling pathway might play a major role in citrate-stabilized AuNRs-induced osteogenic differentiation in MC3T3-E1 cells.…”

Exosome: A Novel Nanocarrier Delivering Noncoding RNA for Bone Tissue Engineering

“…miRNA-214, involved in bone remodeling, adjusts Osterix and activates transcription factor (ATF) 4, which is an essential transcription factor in osteogenesis process [41,42]. Higher levels of miRNA-214 were noted in the plasma of fractured elderly women and ovariectomized mouse.…”

Neuroprotection of N-benzyl Eicosapentaenamide in Neonatal Mice Following Hypoxic–Ischemic Brain Injury

“…A variety of components with pharmacological and nutritional effects have been identified in maca, which include polysaccharides, phytosterols, alkaloids, glucosinolates, macaenes, and macamides [ 11 , 12 ]. Among these bioactive ingredients, macamides, a group of non-polar, long-chain fatty acid N-benzylamide compounds, were recognized as the characteristic constituents while contributing to the major efficacies in maca such as antifatigue, antiosteoporosis, and improving fertility [ 13 , 14 , 15 ]. Macamides and their synthetic analogues have recently been reported to display distinct fatty acid amide hydrolase (FAAH) inhibitory activity, which implies that these compounds possess potential neuroprotective and anti-inflammatory activities [ 16 , 17 ].…”