Chulabhorn International College of Medicine, Thammasat University, Rangsit campus, Pathumthani, 12121, Thailand.
Division of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani, 12121, Thailand.
Sci Rep. 2024 Nov 2;14(1):26415. doi: 10.1038/s41598-024-77850-4.
The present medical treatments of osteoporosis come with adverse effects. It leads to the exploration of natural products as safer alternative medical prevention and treatment. The sea cucumber, Holothuria scabra, has commercial significance in Asian countries with rising awareness of its properties as a functional food. This study aims to investigate the effects of the inner wall (IW) extract isolated from H. scabra on extracellular matrix maturation, mineralization, and osteogenic signaling pathways on MC3T3-E1 preosteoblasts. The IW showed the expression of several growth factors. Molecular docking revealed that H. scabra BMP2/4 binds specifically to mammal BMP2 type I receptor (BMPR-IA). After osteogenic induction, the viability of cells treated with IW extract was assessed and designated with treatment of 0.1, 0.5, 1, and 5 µg/ml of IW extract for 21 consecutive days. On days 14 and 21, treatments with IW extract at 1 and 5 µg/ml showed increased alkaline phosphatase (ALP) activity and calcium deposit levels in a dose-dependent manner compared to the control group. Moreover, the transcriptomic analysis of total RNA of cells treated with 5 µg/ml of IW extract exhibited upregulation of TGF-β, PI3K/Akt, MAPK, Wnt and PTH signaling pathways at days 14. This study suggests that IW extract from H. scabra exhibits the potential to enhance osteogenic differentiation and mineralization of MC3T3-E1 preosteoblasts through TGF-β, PI3K/Akt, MAPK, Wnt and PTH signaling pathways. Further investigation into the molecular mechanisms underlying the effect of IW extract on osteogenesis is crucial to support its application as a naturally derived supplement for prevention or treatment of osteoporosis.
目前骨质疏松症的治疗方法存在副作用。因此，人们开始探索天然产物作为更安全的替代医学预防和治疗方法。海参在亚洲国家具有商业意义，人们越来越意识到它作为功能性食品的特性。本研究旨在探讨棘皮动物海参的内壁（IW）提取物对 MC3T3-E1 前成骨细胞细胞外基质成熟、矿化和成骨信号通路的影响。IW 显示出多种生长因子的表达。分子对接表明，H. scabra BMP2/4 特异性结合哺乳动物 BMP2 型 I 受体（BMPR-IA）。在成骨诱导后，评估用 IW 提取物处理的细胞活力，并将处理浓度指定为 0.1、0.5、1 和 5μg/ml 的 IW 提取物连续处理 21 天。在第 14 天和第 21 天，与对照组相比，1μg/ml 和 5μg/ml 的 IW 提取物处理组的碱性磷酸酶（ALP）活性和钙沉积水平呈剂量依赖性增加。此外，用 5μg/ml 的 IW 提取物处理细胞的总 RNA 的转录组分析显示，在第 14 天，TGF-β、PI3K/Akt、MAPK、Wnt 和 PTH 信号通路的转录本上调。本研究表明，H. scabra 的 IW 提取物通过 TGF-β、PI3K/Akt、MAPK、Wnt 和 PTH 信号通路，显示出增强 MC3T3-E1 前成骨细胞成骨分化和矿化的潜力。进一步研究 IW 提取物对成骨作用的分子机制对于支持其作为预防或治疗骨质疏松症的天然衍生补充剂的应用至关重要。
