Sims Stephen M, Panupinthu Nattapon, Lapierre Danielle M, Pereverzev Alexey, Dixon S Jeffrey
Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
Biochim Biophys Acta. 2013 Jan;1831(1):109-16. doi: 10.1016/j.bbalip.2012.08.001. Epub 2012 Aug 7.
Osteoclasts (bone resorbing cells) and osteoblasts (bone forming cells) play essential roles in skeletal development, mineral homeostasis and bone remodeling. The actions of these two cell types are tightly coordinated, and imbalances in bone formation and resorption can result in disease states, such as osteoporosis. Lysophosphatidic acid (LPA) is a potent bioactive phospholipid that influences a number of cellular processes, including proliferation, survival and migration. LPA is also involved in wound healing and pathological conditions, such as tumor metastasis and autoimmune disorders. During trauma, activated platelets are likely a source of LPA in bone. Physiologically, osteoblasts themselves can also produce LPA, which in turn promotes osteogenesis. The capacity for local production of LPA, coupled with the proximity of osteoblasts and osteoclasts, leads to the intriguing possibility that LPA acts as a paracrine mediator of osteoblast-osteoclast signaling. Here we summarize emerging evidence that LPA enhances the differentiation of osteoclast precursors, and regulates the morphology, resorptive activity and survival of mature osteoclasts. These actions arise through stimulation of multiple LPA receptors and intracellular signaling pathways. Moreover, LPA is a potent mitogen implicated in promoting the metastasis of breast and ovarian tumors to bone. Thus, LPA released from osteoblasts is potentially an important autocrine and paracrine mediator - physiologically regulating skeletal development and remodeling, while contributing pathologically to metastatic bone disease. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.
破骨细胞（骨吸收细胞）和成骨细胞（骨形成细胞）在骨骼发育、矿物质稳态和骨重塑过程中发挥着重要作用。这两种细胞类型的作用紧密协调，骨形成与吸收的失衡会导致诸如骨质疏松症等疾病状态。溶血磷脂酸（LPA）是一种强效生物活性磷脂，可影响许多细胞过程，包括增殖、存活和迁移。LPA还参与伤口愈合以及肿瘤转移和自身免疫性疾病等病理状况。在创伤过程中，活化的血小板可能是骨骼中LPA的来源。在生理状态下，成骨细胞自身也能产生LPA，进而促进骨生成。LPA的局部产生能力，加上成骨细胞与破骨细胞的邻近性，引发了一种有趣的可能性，即LPA作为成骨细胞 - 破骨细胞信号传导的旁分泌介质发挥作用。在此，我们总结了新出现的证据，表明LPA可增强破骨细胞前体的分化，并调节成熟破骨细胞的形态、吸收活性和存活。这些作用是通过刺激多种LPA受体和细胞内信号通路产生的。此外，LPA是一种强效促分裂原，与促进乳腺癌和卵巢癌向骨转移有关。因此，成骨细胞释放的LPA可能是一种重要的自分泌和旁分泌介质——在生理上调节骨骼发育和重塑，同时在病理上促成转移性骨病。本文是名为《溶血磷脂研究进展》特刊的一部分。
