人體骨骼的建構與骨質的平衡主要由造骨細胞 (osteoblast)及蝕骨細胞(osteoclast)負責，兩者細胞具備體內恆定 (homeostasis)效應，並與細胞外基質 (extracellular matrix)連結形成骨骼系統，而當骨組織的代謝發生失衡將引發骨頭疾病，包括骨質疏鬆症、骨關節炎、骨頭畸形、類風溼性關節炎等。矽 (silicon, Si)屬於超微量元素，過去研究已指出矽元素具有維持及改善結締組織、關節、骨頭及皮膚等結構完整的功能，在動物和人體試驗結果顯示矽元素的補充可增加骨頭礦物質密度，並能改善骨質強度。然而，目前探討矽元素對於骨質流失的研究甚少，機制同樣未明。本研究團隊製作一種高吸收率的矽素液劑 (rice husk silica liquid, RHSL)，是來自稻殼提取的二氧化矽經鹼溶後的液態劑型，目前已知RHSL可能作為細胞自噬 (autophagy)增強劑的潛力。近年研究發現造骨細胞與蝕骨細胞的骨平衡效益，和細胞內自噬作用 (autophagy)調節可能關係密切，因此本論文欲研究 RHSL 是否影響蝕骨細胞分化，並探討如何透過細胞內機轉及細胞自噬來影響細胞的分化。本研究以 RAW264.7 巨噬細胞 (後續以 RAW 細胞表示)作為分化基礎模式，以 RANKL (Receptor activator of nuclear factor-κB ligand)及 M-CSF (Macrophage colony stimulating factor)誘發 RAW 細胞分化成蝕骨細胞，分化過程加入不同濃度 RHSL 檢測蝕骨細胞分化的改變。結果顯示蝕骨細胞的數量會隨著 RHSL 處理濃度上升而減少 (矽素濃度 25-100 μg/mL)；透過西方點墨法分析發現 RHSL 處理明顯降低 ERK 與 AKT 蛋白質磷酸化，卻提高 JNK 蛋白質磷酸化。另外，利用自噬體染色 (acridine orange)則發現 RHSL 會增加自噬作用，具劑量效應，推測 RHSL 藉由提高 JNK 來促進蝕骨細胞自噬作用，因此減少蝕骨細胞的分化。根據本研究結果， RHSL 具有抑制蝕骨細胞形成的能力，未來可能作為改善骨質代謝疾病的潛力元素，值得更多研究支持。

The construction of the human skeletal system and the balance of bone quality are primarily regulated by osteoblasts and osteoclasts, two types of cells that maintain homeostasis within the body. These cells form the skeletal system by connecting with the extracellular matrix. Imbalances in bone tissue metabolism can lead to various bone disorders, including osteoporosis, osteoarthritis, bone deformities, and rheumatoid arthritis. Silicon (Si) is considered a trace element, and past research has indicated its role in maintaining and improving the integrity of connective tissues, joints, bones, and skin. Animal and human experiments have shown that supplementing silicon can increase bone mineral density and enhance bone strength. However, there is limited research on the impact of silicon on bone loss, and the underlying mechanisms remain unclear. Our research team has developed a high-absorption silicon solution called rice husk silica liquid (RHSL), derived from alkaline-treated silicon dioxide extracted from rice husks. Currently, RHSL is being explored for its potential as an enhancer of cellular autophagy. Recent studies have suggested a close relationship between the benefits of bone balance with osteoblasts and osteoclasts and the regulation of cellular autophagy. Therefore, this study aims to investigate whether RHSL influences osteoclast differentiation and explore the mechanisms by which it affects cellular differentiation through intracellular pathways and autophagy. In this study, RAW264.7 macrophage cells (referred to as RAW cells) were used as a differentiation model. RANKL (Receptor activator of nuclear factor-κB ligand) and M-CSF (Macrophage colony-stimulating factor) were employed to induce the differentiation of RAW cells into osteoclasts, and different concentrations of RHSL were added during the differentiation process to assess changes in differentiation. The results showed that the number of differentiated osteoclasts decreased with increasing RHSL concentrations (silicon concentration 25-100 μg/mL). Western blot analysis revealed that RHSL treatment significantly reduced the phosphorylation of ERK and AKT proteins while increasing the phosphorylation of JNK protein. Additionally, acridine orange staining for autophagosomes indicated that RHSL increased autophagy in a dose-dependent manner. It is suggested that RHSL promotes osteoclast autophagy by upregulating JNK, thereby suppressing osteoclast differentiation. Based on the findings of this study, RHSL demonstrates the ability to inhibit osteoclast formation and may serve as a potential element for improving bone metabolism disorders. Further research is warranted to support these promising results.

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