Prediction of a Potential Mechanism of Intervertebral Disc Degeneration Based on a Novel Competitive Endogenous RNA Network

Figure 6

Schematic diagram of hyaluronic acid-related IDD molecular mechanism. The integral membrane dual-action glycosyltransferase proteins hyaluronan synthases 1–3 (HAS1-3) mediate the polymerization of glucuronic acid (GlcA) with N-acetylglucosamine (GlcNAc) to form HA. The resulting polymer has the arrangement [-4GlcA-1,3GlcNAc-]n. LYVE1, HMMR, STAB2, and CD44 together form the HAR complex. High molecular weight HA is tethered to the cell surface by HA receptors and the GPI-linked hyaluronidase 2 (HYAL2) to form a HA : HAR : HYAL2 complex in the plasma membrane that localizes to caveolae, continuing to complete the degradation of HA. In the acidic environment of the lysosome, hyaluronidase 1 (HYAL1) could hydrolyze large 50 disaccharide unit HA fragments to 2 disaccharide units. HAS2, HYAL1, and LYVE1 may be negatively regulated by miR-4741, while mi663ahg/HEIH (lncRNA) and hsa-circ-0003600 (circRNA) may competitively be bound on miR-4741 to act as ceRNAs, correcting the negative regulation of miR-4741 to prevent IDD.