a Guanghua School of Stomatology, Hospital of Stomatology , Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology , Guangzhou , Guangdong , P.R. China.
b Guangdong Traditional Medical and Sports Injury Rehabilitation Research Institute , Guangdong Second Provincial General Hospital , Guangzhou , Guangdong , P.R. China.
Connect Tissue Res. 2019 Mar;60(2):85-94. doi: 10.1080/03008207.2018.1439485. Epub 2018 Mar 16.
Lysophosphatidic acid is a serum-derived growth factor that is involved in wound healing. Although in its infancy, a growing body of evidence has demonstrated that lysophosphatidic acid exerts a potentially significant role in regulating bone cell biology. However, previous studies mainly focused on the osteoinductive potential of lysophosphatidic acid, its effects on bone tissue vascularization, another essential element during bone regeneration, remains ill-defined so far. Here in this study, we examined the effects of lysophosphatidic acid on osteogenic differentiation as well as the angiogenesis-inducing capacity of pre-osteoblasts, a cell population that coordinates osteogenic and angiogenic processes in bone regenerating niche. Our results showed that treatment of MC3T3-E1 pre-osteoblastic cells with lysophosphatidic acid enhanced alkaline phosphatase activity and matrix mineralization, demonstrating in vitro osteoblastic differentiation. Of particular importance was the finding that vascular endothelial growth factor secretion also increased after lysophosphatidic acid treatment. Lysophosphatidic acid conditioned media of MC3T3-E1 cells was capable of promoting angiogenic behavior of endothelial cells, as evidenced by stimulating proliferation, migration, and tube formation. Besides, inhibition of LPA1/3 receptor abolished lysophosphatidic acid-induced elevation of the osteogenic and angiogenic capability of pre-osteoblasts. Our research demonstrated the important role of lysophosphatidic acid in coupling osteogenesis and angiogenesis during bone remodeling through orchestrating pre-osteoblast behavior, and implications therein for novel and effective treatment strategies for bone regeneration success.
溶血磷脂酸是一种血清来源的生长因子，参与伤口愈合。尽管处于起步阶段，但越来越多的证据表明，溶血磷脂酸在调节骨细胞生物学方面发挥着潜在的重要作用。然而，以前的研究主要集中在溶血磷脂酸的成骨诱导潜力上，其对骨组织血管生成的影响——这是骨再生过程中的另一个重要元素——迄今为止仍未明确界定。在这项研究中，我们研究了溶血磷脂酸对成骨细胞分化以及前成骨细胞的血管生成诱导能力的影响，前成骨细胞是一种协调骨生成和血管生成过程的细胞群体，存在于骨再生龛中。我们的结果表明，溶血磷脂酸处理 MC3T3-E1 前成骨细胞可增强碱性磷酸酶活性和基质矿化，表明体外成骨细胞分化。特别重要的是发现血管内皮生长因子的分泌也增加了溶血磷脂酸处理后。MC3T3-E1 细胞的溶血磷脂酸条件培养基能够促进内皮细胞的血管生成行为，这表现在刺激增殖、迁移和管形成方面。此外，LPA1/3 受体的抑制作用消除了溶血磷脂酸诱导的前成骨细胞成骨和血管生成能力的升高。我们的研究表明，溶血磷脂酸通过协调前成骨细胞的行为，在骨重塑过程中在成骨和血管生成之间起着重要作用，这对骨再生成功的新的有效治疗策略具有重要意义。
