溶血磷脂酸诱导的YAP活化调节MC3T3-E1的成骨作用

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-08-28 DOI:10.1016/j.tice.2025.103111

Qin Zhang , Jiayi Liu , Bingfeng Wu , Ying Yuan , Ping Gong , Lin Xiang

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引用次数: 0

摘要

溶血磷脂酸（LPA）是一种小生物活性溶血磷脂，在骨稳态和疾病中引起多种生物活性。然而，LPA的具体功能和这些过程的内在机制尚不清楚。在这项研究中，我们发现LPA主要通过LPA1在MC3T3-E1前成骨细胞中调节细胞增殖、迁移和成骨分化。更重要的是，western blot分析表明，LPA通过Hippo通路激活LATS，刺激转录调节因子YAP的激活，但对MST的影响可以忽略不计。此外，应用椎泊芬阻断YAP，进一步阐明了lpa诱导的YAP激活对成骨的影响。有趣的是，rho激酶（ROCK）也可能参与lpa诱导的YAP核定位和去磷酸化。综上所述，这些数据为LPA在骨稳态和再生中的分子机制提供了新的见解。

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Lysophosphatidic acid-induced YAP activation regulates osteogenesis of MC3T3-E1

Lysophosphatidic acid (LPA) is a small bioactive lysophospholipid that elicits diverse biological activities in bone homeostasis and diseases. However, the specific functions of LPA and intrinsic mechanism underlying these processes is not well understood. In this study, we identified that LPA regulated cell proliferation, migration, and osteogenic differentiation primarily via LPA₁ in MC3T3-E1 pre-osteoblastic cells. More importantly, western blot analysis indicated that LPA stimulated the activation of the transcriptional regulator YAP via the Hippo pathway kinases LATS, but had negligible effects on MST. Moreover, verteporfin was applied to block YAP, which further elucidated the effects of LPA-induced YAP activation on osteogenesis. Interestingly, Rho-kinase (ROCK) might also be involved in LPA-induced YAP nuclear localization and dephosphorylation. Taken together, these data provide novel insights into the molecular mechanisms of LPA in bone homeostasis and regeneration.

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.