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The effects of fucoxanthin on proliferation and osteogenic differentiation of human mesenchymal stem cell under oxidative stress conditions |
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| รหัสดีโอไอ | |
| Title | The effects of fucoxanthin on proliferation and osteogenic differentiation of human mesenchymal stem cell under oxidative stress conditions |
| Creator | Gunticha Suwanmanee |
| Contributor | Sirikul Manochantr, Advisor |
| Publisher | Thammasat University |
| Publication Year | 2568 |
| Keyword | Fucoxanthin, Mesenchymal stem cells, Placenta, Oxidative stress, Antioxidant, Apoptosis, ฟิวโคแซนทิน, เซลล์ต้นกำเนิดมีเซนไคม์, รก, ภาวะเครียดออกซิเดชั่น, สารต้านอนุมูลอิสระ, การตายของเซลล์แบบอะพอพโทซิส |
| Abstract | Osteoporosis, a bone disorder marked by diminished bone mass and elevated fracture risk, has emerged as a major and expanding public health concern, significantly affecting quality of life through its medical, social, and economic aspects. It is closely linked to oxidative stress and reactive oxygen species (ROS). These factors disrupt bone homeostasis by accelerating bone resorption and suppressing bone formation. Specifically, oxidative stress triggers osteoclast differentiation and osteocyte apoptosis while inhibiting osteoblast activity. Nevertheless, the mechanisms that collectively drive metabolic bone disorders and contribute to the pathogenesis of osteoporosis are unclear. Current therapeutic strategies for the management of osteoporosis are often limited by significant adverse effects. Fucoxanthin, a marine carotenoid derived from brown algae, exhibits potent antioxidant activity, including the enhancement of antioxidant enzyme production and the reduction of ROS levels. This study investigates the potential of fucoxanthin to modulate cell viability, apoptotic processes, and osteogenic differentiation capacity in placenta-derived mesenchymal stem cells (PL-MSCs) exposed to oxidative stress conditions. The first phase evaluated the effects of fucoxanthin on cell viability, apoptosis, and antioxidant responses in PL-MSCs exposed to hydrogen peroxide (H2O2). PL MSCs treated with 1-5 µM fucoxanthin, either concurrently (co-treatment) or before (pre-treatment) H2O2 exposure, showed restored viability and proliferation as evidenced by increased cyclin D1 expression. Fucoxanthin also upregulated antioxidant enzymes, decreased intracellular ROS, and reduced apoptosis markers, partly via activation of the PI3K/Akt/Nrf2 pathway. High-throughput gene expression profiling indicated that fucoxanthin modulates survival pathways, DNA repair, and suppresses apoptosis-related processes.The second phase assessed the effects of fucoxanthin on the osteogenic differentiation of PL-MSCs under oxidative stress. PL-MSCs cultured in osteogenic induction medium with H2O2 and 1-3 µM fucoxanthin exhibited enhanced alkaline phosphatase activity, matrix mineralization, and expression of osteogenic markers. The Wnt/ß-catenin signaling pathway was implicated, as DKK-1 inhibition diminished the pro-osteogenic effects of fucoxanthin.In summary, fucoxanthin confers cytoprotective effects on PL-MSCs by mitigating oxidative damage through the PI3K/Akt/Nrf-2 pathway and enhances osteogenic differentiation through Wnt/ß-catenin signaling. These findings suggest that fucoxanthin holds promise as a therapeutic agent for the prevention or treatment of osteoporosis |
