Lin Shaozi, Meng Zuyu, Wang Mei, Ye Zixuan, Long Mengsha, Zhang Yiyao, Liu Fang, Chen Hongling, Li Menghan, Qin Jiajia, Liu Haiquan
School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
Huizhou Hospital, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Front Pharmacol. 2025 Jan 13;15:1510561. doi: 10.3389/fphar.2024.1510561. eCollection 2024.
Adipose-derived stem cell (ADSC) transplantation presents a promising approach for osteoporosis (OP) treatment. However, the therapeutic efficacy of ADSCs is hindered by low post-transplantation survival rates and limited capacities for adhesion, migration, and differentiation. Icariin (ICA), the primary active compound of Epimedium, has been shown to promote cell proliferation and induce osteogenic differentiation; however, its specific effects on ADSC osteogenesis and the mechanisms by which ICA enhances osteoporosis treatment through cell transplantation remain inadequately understood.
This study investigates the effects of different concentrations of ICA on the osteogenic and adipogenic differentiation of rat ADSCs, aiming to elucidate the underlying mechanisms. ADSCs were isolated from female SPF-grade SD rats, with surface markers identified through flow cytometry. Osteogenic and adipogenic differentiation were assessed using Alizarin Red and Oil Red O staining, respectively. Third-generation ADSCs were divided into five groups: control, resveratrol (100 μmol/L), and four ICA treatment groups (1, 10, 50, and 100 μmol/L). Western blotting was performed to analyze the expression of factors associated with the Hippo-YAP/TAZ signaling pathway and the adipogenic marker PPARγ. Additionally, ADSCs were labeled with lentiviruses carrying enhanced green fluorescent protein (EGFP) and 5-bromo-2-deoxyuridine (BrdU) to assess their distribution, survival, proliferation, and differentiation of ADSCs post-ICA intervention.
, ICA significantly inhibited the Hippo pathway, reducing YAP and TAZ phosphorylation and enhancing their transcriptional activity, while simultaneously suppressing PPARγ. This promoted osteogenesis and inhibited adipogenesis in ADSCs. , ICA-treated ADSCs demonstrated effective distribution, survival, and osteogenic differentiation following subcutaneous injection into allogeneic rats.
Our study demonstrates that ICA significantly enhances the osteogenic differentiation of ADSCs while inhibiting adipogenesis, providing novel insights and therapeutic strategies for osteoporosis and related conditions.
脂肪来源干细胞（ADSC）移植是一种很有前景的骨质疏松症（OP）治疗方法。然而，ADSCs的治疗效果受到移植后存活率低以及粘附、迁移和分化能力有限的阻碍。淫羊藿苷（ICA）是淫羊藿的主要活性成分，已被证明可促进细胞增殖并诱导成骨分化；然而，其对ADSC成骨的具体作用以及ICA通过细胞移植增强骨质疏松症治疗的机制仍未得到充分了解。
本研究探讨不同浓度ICA对大鼠ADSCs成骨和成脂分化的影响，旨在阐明其潜在机制。从雌性SPF级SD大鼠中分离ADSCs，通过流式细胞术鉴定表面标志物。分别使用茜素红和油红O染色评估成骨和成脂分化。将第三代ADSCs分为五组：对照组、白藜芦醇（100 μmol/L）组和四个ICA治疗组（1、10、50和100 μmol/L）。进行蛋白质免疫印迹分析与Hippo-YAP/TAZ信号通路相关的因子以及成脂标志物PPARγ的表达。此外，用携带增强型绿色荧光蛋白（EGFP）和5-溴-2-脱氧尿苷（BrdU）的慢病毒标记ADSCs，以评估ICA干预后ADSCs的分布、存活、增殖和分化。
ICA显著抑制Hippo通路，降低YAP和TAZ磷酸化并增强其转录活性，同时抑制PPARγ。这促进了ADSCs的成骨作用并抑制了成脂作用。皮下注射到同种异体大鼠后，经ICA处理的ADSCs表现出有效的分布、存活和成骨分化。
我们的研究表明，ICA显著增强ADSCs的成骨分化，同时抑制成脂作用，为骨质疏松症及相关病症提供了新的见解和治疗策略。
