Marine Biotechnology Center for Pharmaceuticals and Foods, College of Medical and Life Sciences, Silla University, Busan 46958, Korea.
Division of Marine Bioscience, Korea Maritime and Ocean University, Busan 49112, Korea.
Phytomedicine. 2020 Jun;71:153225. doi: 10.1016/j.phymed.2020.153225. Epub 2020 May 15.
Impaired bone formation is one of the reasons behind osteoporosis. Alterations in the patterns of mesenchymal stromal cell differentiation towards adipocytes instead of osteoblasts contribute to osteoporosis progression. Natural anti-osteoporotic agents are effective and safe alternatives for osteoporosis treatment.
In this context, 3,5-dicaffeoyl‑epi-quinic acid (DCEQA) which is a derivative of chlorogenic acid with reported bioactivities was studied for its osteogenic differentiation enhancing potential in vitro.
Anti-osteoporotic effects of DCEQA were investigated in human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) which were induced to differentiate into osteoblasts or adipocytes with or without DCEQA treatment. Changes in the osteogenic and adipogenic markers such as ALP activity and lipid accumulation, respectively, were observed along with differentiation-specific activation of mitogen activated protein kinase (MAPK) pathways.
At 10 μM concentration, DCEQA increased the proliferation of bone marrow-derived human mesenchymal stromal cells (hBM-MSCs) during osteoblast differentiation. The expression of osteogenic markers ALP, osteocalcin, Runx2, BMP2 and Wnt 10a was upregulated by DCEQA treatment. The ALP activity and extracellular mineralization were also increased. DCEQA elevated the phosphorylation levels of p38 and JNK MAPKs as well as the activation of β-catenin and Smad1/5. DCEQA suppressed the lipid accumulation and downregulated expression of adipogenic markers PPARγ, C/EBPα and SREBP1c in adipo-induced hBM-MSCs. DCEQA also decreased the phosphorylation of p38 and ERK MAPKs and stimulated the activation of AMPK in hBM-MSC adipocytes.
DCEQA was suggested to enhance osteoblast differentiation via stimulating Wnt/BMP signaling. The adipocyte differentiation inhibitory effect of DCEQA was suggested to arise from its ability to increase AMPK phosphorylation. Overall, DCEQA was shown to possess osteogenesis enhancing and adipogenesis inhibitory properties which might facilitate its use against osteoporotic conditions.
骨形成受损是骨质疏松症的原因之一。间充质基质细胞向脂肪细胞而非成骨细胞分化模式的改变导致骨质疏松症的进展。天然抗骨质疏松药物是治疗骨质疏松症的有效和安全替代品。
在这种情况下，具有报道的生物活性的绿原酸衍生物 3,5-二咖啡酰基-表奎尼酸（DCEQA）在体外研究了其促进成骨细胞分化的潜力。
用 DCEQA 处理或不处理，诱导人骨髓间充质基质细胞（hBM-MSCs）分化为成骨细胞或脂肪细胞，研究 DCEQA 的抗骨质疏松作用。观察碱性磷酸酶（ALP）活性和脂质积累等成骨和脂肪形成标记物的变化，以及有丝分裂原激活蛋白激酶（MAPK）途径的分化特异性激活。
在 10 μM 浓度下，DCEQA 增加了成骨细胞分化过程中骨髓源性人间充质基质细胞（hBM-MSCs）的增殖。DCEQA 处理上调了成骨标志物 ALP、骨钙素、Runx2、BMP2 和 Wnt10a 的表达。ALP 活性和细胞外矿化也增加。DCEQA 升高了 p38 和 JNK MAPK 的磷酸化水平以及β-catenin 和 Smad1/5 的激活。DCEQA 抑制了脂滴积累并下调了脂肪诱导的 hBM-MSCs 中脂肪形成标志物 PPARγ、C/EBPα 和 SREBP1c 的表达。DCEQA 还降低了 p38 和 ERK MAPK 的磷酸化水平，并刺激了 hBM-MSC 脂肪细胞中 AMPK 的激活。
DCEQA 被认为通过刺激 Wnt/BMP 信号增强成骨细胞分化。DCEQA 抑制脂肪细胞分化的作用可能源于其增加 AMPK 磷酸化的能力。总的来说，DCEQA 表现出增强成骨和抑制脂肪形成的特性，这可能有助于其在骨质疏松症中的应用。
