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Review
. 2015 Mar;72(5):959-69.
doi: 10.1007/s00018-014-1778-x. Epub 2014 Nov 26.

Sphingolipid metabolism and its role in the skeletal tissues

Zohreh Khavandgar  1 , Monzur Murshed
Affiliations
Review

Sphingolipid metabolism and its role in the skeletal tissues

Zohreh Khavandgar et al. Cell Mol Life Sci. 2015 Mar.

Abstract

The regulators affecting skeletal tissue formation and its maintenance include a wide array of molecules with very diverse functions. More recently, sphingolipids have been added to this growing list of regulatory molecules in the skeletal tissues. Sphingolipids are integral parts of various lipid membranes present in the cells and organelles. For a long time, these macromolecules were considered as inert structural elements. This view, however, has radically changed in recent years as sphingolipids are now recognized as important second messengers for signal-transduction pathways that affect cell growth, differentiation, stress responses and programmed death. In the current review, we discuss the available data showing the roles of various sphingolipids in three different skeletal cell types-chondrocytes in cartilage and osteoblasts and osteoclasts in bone. We provide an overview of the biology of sphingomyelin phosphodiesterase 3 (SMPD3), an important regulator of sphingolipid metabolism in the skeleton. SMPD3 is localized in the plasma membrane and has been shown to cleave sphingomyelin to generate ceramide, a bioactive lipid second messenger, and phosphocholine, an essential nutrient. SMPD3 deficiency in mice impairs the mineralization in both cartilage and bone extracellular matrices leading to severe skeletal deformities. A detailed understanding of SMPD3 function may provide a novel insight on the role of sphingolipids in the skeletal tissues.

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Figures

Fig. 1
Fig. 1
Chemical structures of sphingosine and its derivatives ceramide and sphingomyelin. A ceramide molecule is composed of sphingosine and a fatty acid (green) linked by an amide bond. An enzymatic addition of a phosphocholine head group (blue) to a ceramide molecule leads to the synthesis of sphingomyelin
Fig. 2
Fig. 2
De novo and sphingomyelinase pathways showing the metabolism of ceramide, sphingomyelin and sphingosine
Fig. 3
Fig. 3
The major effects of ceramide (a) and Sphingosine 1 phosphate (S1P) (b) on osteoblasts, chondrocytes and osteoclasts. The filled up arrows indicate activation and the filled down arrows indicate inhibition
Fig. 4
Fig. 4
Abnormal presence of cartilage matrix and chondrocytes asterisk in a fro/fro developing humerus from an E15.5 embryo. The histological sections were stained with Safranin O
See this image and copyright information in PMC

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