The emerging role of lysophosphatidic acid (LPA) in skeletal biology

Lysophosphatidic acid (LPA) is the simplest signalling lipid eliciting pleiotropic actions upon most mammalian cell types. Although LPA has an established role in many biological processes, particularly wound healing and cancer, the participation of LPA in skeletal biology is just beginning to emerge. Early studies, identified in this review, gave a solid indication that LPA, via binding to one of several cell surface receptors, activated multiple intracellular systems culminating in altered cell morphology, growth, motility and survival. More recently the ablation of murine LPA1 and 4 receptors implies that this lipid has a role in skeletal development and post natal bone accrual. Greater understanding of the ability of LPA to influence, for example, osteoblast growth, maturation and survival could be advantageous in developing novel strategies aimed at improving skeletal tissue repair and regeneration. Herein this review provides an insight into the diversity of studies exploring the actions of a small lipid on those major cell types key to skeletal tissue health and homeostasis.

► Cell surface receptors for LPA have been identified for most skeletal cell types.
► LPA influences the growth, migration, morphology and maturation of these cells.
► LPA appears to have a role in skeletogenesis via LPA receptors 1 and 4.
► LPA co-operates with calcitriol to enhance human osteoblastogenesis and maturation.
► Selected LPA receptor ligands may find a role in bone repair and regeneration.