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| 磷酸酶张力蛋白同源物在骨质疏松症中机制与调控 |
| The mechanism and intervention of phosphatase tensin homologs in osteoporosis |
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| DOI：10.3969/j.issn.1006-7108.2026.05.017 |
| 中文关键词: 骨质疏松症 磷酸酶张力蛋白同源物 抑癌基因 磷酸酶 骨代谢 |
| 英文关键词:osteoporosis phosphatase tensin homolog tumor suppressor gene phosphatase enzyme bone metabolism |
| 基金项目:甘肃省自然科学基金（22JR5RA624） |
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| 中文摘要: |
| 骨质疏松症的核心机制在于成骨-破骨动态平衡失调，而磷酸酶张力蛋白同源物 (phosphatase and tensin homolog，PTEN)在骨代谢中具有关键作用。PTEN表达异常可通过多种途径抑制成骨活性并促进破骨功能。首先，PTEN可通过拮抗PI3K/Akt/mTOR通路调控成骨细胞，其异常活化可加剧氧化应激及成骨细胞凋亡，同时加速破骨前体细胞分化。此外，PTEN与Wnt/β-catenin通路的交互调控显著影响骨形成。PTEN通过去磷酸化β-catenin促进其降解，抑制成骨基因表达，激活Wnt信号。因此，调节Nrf2/HO-1抗氧化通路或抑制NF-κB炎症信号可改善PTEN异常引起的成骨障碍。PTEN还可通过调节Src激酶活性影响皮肤源性因子胱抑素-A介导的骨代谢平衡，为跨器官调控骨稳态提供理论依据。因此，PTEN可能是骨代谢的核心调控节点，其靶向干预有望推动骨质疏松症精准治疗的发展。 |
| 英文摘要: |
| The core mechanism of osteoporosis is the imbalance of osteogenic osteoclast dynamics. Phosphatase and tensin homolog (PTEN) plays a key role in bone metabolism. Abnormal expression of PTEN inhibits osteogenic activity and promotes osteoclast function through various pathways. Firstly, PTEN regulates osteoblasts by antagonizing the PI3K/Akt/mTOR pathway, and its abnormal activation exacerbates oxidative stress and osteoblast apoptosis, while accelerating osteoclast precursor cell differentiation. In addition, the interaction regulation between PTEN and Wnt/β - catenin pathway significantly affects bone formation. PTEN promotes its degradation by dephosphorylating β - catenin, inhibits osteogenic gene expression, and activates Wnt signaling. Therefore, regulating the Nrf2/HO-1 antioxidant pathway or inhibiting NF-κ B inflammatory signaling improves osteogenic disorders caused by PTEN abnormalities. PTEN also affects the bone metabolism balance mediated by the skin derived factor cystatin A by regulating Src kinase activity, providing a theoretical basis for cross organ regulation of bone homeostasis. Therefore, PTEN may be the core regulatory node of bone metabolism. Its targeted intervention is expected to promote the development of precise treatment for osteoporosis. |
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