Phospholipases of Mineralization Competent Cells and Matrix Vesicles: Roles in Physiological and Pathological Mineralizations

Abstract

The present review aims to systematically and critically analyze the current knowledge on phospholipases and their role in physiological and pathological mineralization undertaken by mineralization competent cells. Cellular lipid metabolism plays an important role in biological mineralization. The physiological mechanisms of mineralization are likely to take place in tissues other than in bones and teeth under specific pathological conditions. For instance, vascular calcification in arteries of patients with renal failure, diabetes mellitus or atherosclerosis recapitulates the mechanisms of bone formation. Osteoporosis—a bone resorbing disease—and rheumatoid arthritis originating from the inflammation in the synovium are also affected by cellular lipid metabolism. The focus is on the lipid metabolism due to the effects of dietary lipids on bone health. These and other phenomena indicate that phospholipases may participate in bone remodelling as evidenced by their expression in smooth muscle cells, in bone forming osteoblasts, chondrocytes and in bone resorbing osteoclasts. Among various enzymes involved, phospholipases A1 or A2, phospholipase C, phospholipase D, autotaxin and sphingomyelinase are engaged in membrane lipid remodelling during early stages of mineralization and cell maturation in mineralization-competent cells. Numerous experimental evidences suggested that phospholipases exert their action at various stages of mineralization by affecting intracellular signaling and cell differentiation. The lipid metabolites—such as arachidonic acid, lysophospholipids, and sphingosine-1-phosphate are involved in cell signaling and inflammation reactions. Phospholipases are also important members of the cellular machinery engaged in matrix vesicle (MV) biogenesis and exocytosis. They may favour mineral formation inside MVs, may catalyse MV membrane breakdown necessary for the release of mineral deposits into extracellular matrix (ECM), or participate in hydrolysis of ECM. The biological functions of phospholipases are discussed from the perspective of animal and cellular knockout models, as well as disease implications, development of potent inhibitors and therapeutic interventions.

Ultrastructural changes during osteogenic differentiation in mesenchymal stromal cells cultured in alginate hydrogel

“…They constitute the one of intercellular communication mechanisms, as it was shown in previous studies [5]. Moreover, numerous observations of Anderson [4, 6–12] and others revealed that similar submicron organelles may be also involved in the process of biomineralization [4, 6–12]. …”

PLA2and ENPP6 may act in concert to generate phosphocholine from the matrix vesicle membrane during skeletal mineralization

“…Multiple PLA 2 isozymes are known to exist in vertebrates, including 31 different isoforms of PLA 2 in humans (28). PLA 2 preferentially acts on phospholipids (including phosphatidylcholine and phosphatidylethanolamine), with arachidonic acid present at the sn-2 position, and thus, the presence of arachidonic acid is an indicator of PLA 2 activity (28,29).…”

“…Multiple PLA 2 isozymes are known to exist in vertebrates, including 31 different isoforms of PLA 2 in humans (28). PLA 2 preferentially acts on phospholipids (including phosphatidylcholine and phosphatidylethanolamine), with arachidonic acid present at the sn-2 position, and thus, the presence of arachidonic acid is an indicator of PLA 2 activity (28,29). The presence of PLA 2 isoforms has been confirmed in chondrocytes, osteoblasts, and cartilage, and these enzymes have also been localized to MVs and associated with matrix mineralization (28,30).…”

“…PLA 2 preferentially acts on phospholipids (including phosphatidylcholine and phosphatidylethanolamine), with arachidonic acid present at the sn-2 position, and thus, the presence of arachidonic acid is an indicator of PLA 2 activity (28,29). The presence of PLA 2 isoforms has been confirmed in chondrocytes, osteoblasts, and cartilage, and these enzymes have also been localized to MVs and associated with matrix mineralization (28,30). Additional investigations have demonstrated that a particular PLA 2 isoform (encoded by the pla2g4a gene) is strongly associated with bone modeling (31).…”

Effects of phospholipase D during cultured osteoblast mineralization and bone formation

“…1 The presence of different isoforms of phospholipase D (PLD) in chondrocytes 2-4 and in osteoblasts [5][6][7][8][9] were previously reported, suggesting that PLD may regulate differentiation, maturation, and function of cells. 1 The presence of different isoforms of phospholipase D (PLD) in chondrocytes 2-4 and in osteoblasts [5][6][7][8][9] were previously reported, suggesting that PLD may regulate differentiation, maturation, and function of cells.…”