Sesamol improves bone mass in ovary intact growing and adult rats but accelerates bone deterioration in the ovariectomized rats

Sesamol, an active component in sesame seeds, is known for its health benefits. However, its effect on bone metabolism remains unexplored. The present study aims to investigate the effect of sesamol on growing, adult and osteoporotic skeleton and its mechanism of action. Sesamol at various doses were administered orally to growing, ovariectomized, and ovary-intact rats. Alterations in bone parameters were examined using micro-CT and histological studies. Western blot and mRNA expression from long bones were performed. We further evaluated the effect of sesamol on osteoblast and osteoclast function and its mode of action in the cell culture system. These data showed that sesamol was able to promote peak bone mass in growing rats. However, sesamol had the opposite effect in ovariectomized rats, evident from gross deterioration of trabecular and cortical microarchitecture. Concurrently, it improved the bone mass in adult rats. In vitro results revealed that sesamol enhances the bone formation by stimulating osteoblast differentiation through MAPK, AKT, and BMP-2 signaling. In contrast, it enhances osteoclast differentiation and expression of osteoclast-specific genes in osteoclast differentiation medium. Interestingly, in presence of estrogen, the effect reversed and sesamol decreased osteoclast differentiation, in vitro. Sesamol improves bone microarchitecture in growing and ovary-intact rats, whereas it enhances the bone deterioration in ovariectomized rats. While sesamol promotes bone formation, its opposing effect on the skeleton can be attributed to its dual effect on osteoclastogenesis in presence and absence of estrogen. These preclinical findings suggest a special attention towards the detrimental effect of sesamol in postmenopausal women.