Physiological Significance of Lysophosphatidic Acid in the Regulation of Inflammatory Bone Diseases
Osteoclasts, bone resorbing cells and osteoblasts, bone forming cells play crucial roles in skeletal development, bone remodeling and mineral homeostasis. Osteoblasts and osteoclast act in a coordinated manner and imbalances of either cell type can lead to bone diseases such as osteoporosis. Lysophosphatidic acid (LPA), a bioactive phospholipid is involved in several bodily processes such as wound healing or tumor metastasis and influences cellular processes such as growth, survival and migration. LPA has recently been discussed by several articles and research studies to play an essential role as a mediator of osteoblast and osteoclast signaling.
A review article by Danielle, et al summarizes evidence that discusses LPA, a bioactive phospholipid and its essential role in the interactions that occur between osteoblasts and osteoclasts. The review article suggests several ways that LPA released from osteoblasts are important mediators of bone growth, survival and calcium levels. No experiments were conducted in this paper as it was a review article discussing LPA’s interaction through several receptors. It is also mentioned in the review that the human body can be vulnerable to bone diseases such as osteoporosis or tumour growth if this acid was inhibited by osteoblasts. Similarly, a research article by Stephen, et al discusses the function of LPA and its role in mediating intercellular signalling among osteoblast and osteoclasts. LPA activity on osteoclasts were studied in vitro in this study and it was determined that LPA interacts through several receptors in order to increase calcium levels and induce prolonged osteoclast survival. It was identified in this study that LPA plays a key role in the mediation of intercellular signalling. This study also determined that LPA can serve as both autocrine and paracrine signaling molecules in the bone microenvironment as they can act by physiologically regulating skeletal development and remodeling.
Both identified articles discuss the essential roles of LPA involving the interactions between osteoblasts and osteoclasts in the bone and how it acts through several receptors on osteoclasts to promote cellular retraction and to elevate calcium and osteoclast survival. The next logical research question that arises is what are the roles of LPA and associated receptors in the regulation of pathological bone loss in inflammatory diseases such as arthritis or rheumatoid? This question can be addressed using an in vivo experiment on the osteoclasts of rabbits with and without arthritis. Osteoclast samples will be collected from rabbits. LPA receptors will be tagged using immunofluorescence