Lysophosphatidic acid enhanced the osteogenic and angiogenic capability of osteoblasts via LPA1/3 receptor

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.