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| 脱氢胆酸调控OPG/RANK和TRAF3抑制破骨细胞分化 |
| Dehydrocholic acid inhibits osteoclast differentiation by regulating OPG/RANK and TRAF3 |
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| DOI：10.3969/j.issn.1006-7108.2024.01.003 |
| 中文关键词: 脱氢胆酸 破骨细胞 OPG/RANK TRAF3 骨质疏松 |
| 英文关键词:dehydrocholic acid osteoclasts OPG/RANK TRAF3 osteoporosis |
| 基金项目:国家重点研发计划（2018YFE0195200） |
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| 中文摘要: |
| 目的 探讨脱氢胆酸（dehydrocholic acid，DHCA）对破骨细胞（osteoclasts，OCs）分化及功能的影响。方法 采用粒细胞-巨噬细胞集落刺激因子和核因子κB受体活化因子配体（receptor activator of nuclear factor kappa B(NF-κB)-ligand，RANKL）诱导成熟骨髓来源的巨噬细胞分化为OCs。通过抗酒石酸酸性磷酸酶（tartrate-resistant acid phosphatase，TRAP/ACP5）染色，确定DHCA抑制OCs形成的最佳浓度。qRT-PCR检测OCs分化和功能相关基因TRAP/ACP5、组织蛋白酶K（cathepsin K，CTSK）和基质金属蛋白酶9（matrix metalloproteinase 9，MMP9）的基因表达。Western blot检测OCs中TNF受体相关因子3（TNF receptor-associated factor 3，TRAF3）、NF-κB受体活化因子（receptor activator of NF-κB，RANK）和骨保护素（osteoprotegerin，OPG）的蛋白水平。结果 DHCA浓度为200 μmol/L是抑制OCs形成的最佳剂量（P＜0.01）。DHCA抑制OCs分化和功能相关基因ACP5、CTSK和MMP9的表达（P＜0.01）。DHCA通过下调RANK蛋白和增加TRAF3和OPG蛋白的表达来抑制OCs的分化（P＜0.01）。 结论 DHCA通过调控OPG/RANK和TRAF3抑制OCs分化，这可能是一种有效的骨质疏松前体药物。 |
| 英文摘要: |
| Objective To investigated the effect of dehydrocholic acid (DHCA) on osteoclast (OCs) differentiation and function. Methods Granulocyte macrophage colony-stimulating factor and receptor activator of nuclear factor kappa B (NF-κB)-ligand (RANKL) were used to differentiate mature bone marrow macrophages into OCs. To determine the best concentration of DHCA to inhibit OC formation, tartrate resistant acid phosphatase (TRAP) staining was conducted. The gene expressions of tartrate-resistant acid phosphatase (TRAP/ACP5), cathepsin K (CTSK), matrix metalloproteinase 9 (MMP9), and OC differentiation- and function-related genes were detected using qRT-PCR. The protein levels of TNF receptor-associated factor 3 (TRAF3), receptor activator of NF-κB (RANK), and osteoprotegerin (OPG) in OCs were measured with Western blotting. Results DHCA at a concentration of 200 μmol/L was the optimal dose to inhibit OC formation in vitro (P<0.01). DHCA inhibited the differentiation- and function-related genes ACP5, CTSK, and MMP9 of OCs (P<0.01). Mechanically, DHCA inhibited OC differentiation by down-regulating RANK proteins and increasing the expression of TRAF3 and OPG proteins (P<0.01). Conclusion DHCA inhibits OC differentiation by regulating OPG/RANK and TRAF3. This may be an effective prodrug for anti-osteoporosis. |
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