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.