Department of Medical, Oral and Biotechnological Sciences, Center for Advanced Studies and Technology-CAST, University G. D'Annunzio of Chieti-Pescara, 66100 Chieti, Italy.
Department of Neurosciences, Imaging and Clinical Sciences, Center for Advanced Studies and Technology-CAST, University G. D'Annunzio of Chieti-Pescara, 66100 Chieti, Italy.
Nutrients. 2022 Aug 5;14(15):3209. doi: 10.3390/nu14153209.
Bone physiology is regulated by osteoblast and osteoclast activities, both involved in the bone remodeling process, through deposition and resorption mechanisms, respectively. The imbalance between these two phenomena contributes to the onset of bone diseases. Among these, osteoporosis is the most common metabolic bone disorder. The therapies currently used for its treatment include antiresorptive and anabolic agents associated with side effects. Therefore, alternative therapeutic approaches, including natural molecules such as coumarin and their derivatives, have recently shown positive results. Thus, our proposal was to investigate the effect of the coumarin derivative umbelliferon (UF) using an interesting model of human osteoblasts (hOBs) isolated from osteoporotic patients. UF significantly improved the activity of osteoporotic-patient-derived hOBs via estrogen receptor 1 (ESR1) and the downstream activation of β-catenin pathway. Additionally, hOBs were co-cultured in microgravity with human osteoclasts (hOCs) using a 3D system bioreactor, able to reproduce the bone remodeling unit in bone loss conditions in vitro. Notably, UF exerted its anabolic role by reducing the multinucleated cells. Overall, our study confirms the potential efficacy of UF in bone health, and identified, for the first time, a prospective alternative natural compound useful to prevent/treat bone loss diseases such as osteoporosis.
骨骼生理学受成骨细胞和破骨细胞活动的调节，这两者都参与了骨重塑过程，分别通过沉积和吸收机制。这两种现象之间的失衡导致了骨骼疾病的发生。其中，骨质疏松症是最常见的代谢性骨骼疾病。目前用于治疗骨质疏松症的疗法包括抗吸收和合成代谢药物，但这些药物都伴随着副作用。因此，最近包括香豆素及其衍生物等天然分子在内的替代治疗方法已经显示出了积极的效果。因此，我们的研究旨在使用来自骨质疏松症患者的人成骨细胞（hOB）的有趣模型来研究香豆素衍生物 Umbelliferon (UF) 的作用。UF 通过雌激素受体 1 (ESR1) 和 β-连环蛋白途径的下游激活显著改善了骨质疏松症患者来源的 hOB 的活性。此外，使用 3D 系统生物反应器将 hOB 与人类破骨细胞（hOC）共培养，该生物反应器能够在体外复制骨丢失条件下的骨重塑单位。值得注意的是，UF 通过减少多核细胞发挥其合成代谢作用。总的来说，我们的研究证实了 UF 在骨骼健康方面的潜在功效，并首次确定了一种有前景的天然化合物替代物，可用于预防/治疗骨质疏松症等骨骼流失疾病。
