Pentosan Polysulfate, a Semisynthetic Heparinoid Disease-Modifying Osteoarthritic Drug with Roles in Intervertebral Disc Repair Biology Emulating the Stem Cell Instructive and Tissue Reparative Properties of Heparan Sulfate

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Abstract
This review highlights the attributes of pentosan polysulphate (PPS) in the promotion of intervertebral disc (IVD) repair processes. PPS has been classified as a disease modifying osteoarthritic drug (DMOAD) and many studies have demonstrated its positive attributes in the countering of degenerative changes occurring in cartilaginous tissues during the development of osteoarthritis (OA). Degenerative changes in the IVD also involve inflammatory cytokines, degradative proteases and cell signalling pathways similar to those operative in the development of OA in articular cartilage. PPS acts as a heparan sulphate (HS) mimetic to effect its beneficial effects in cartilage. The IVD contains small cell membrane HS-proteoglycans (HSPGs) such as syndecan, and glypican and a large multifunctional HS/chondroitin sulphate (CS) hybrid proteoglycan (HSPG2/perlecan) that have important matrix stabilising properties and sequester, control and present growth factors from the FGF, VEGF, PDGF and BMP families to cellular receptors to promote cell proliferation, differentiation and matrix synthesis. HSPG2 also has chondrogenic properties and stimulates the synthesis of extracellular matrix (ECM) components, expansion of cartilaginous rudiments and has roles in matrix stabilisation and repair. Perlecan is a perinuclear and nuclear proteoglycan in IVD cells with roles in chromatin organisation and control of transcription factor activity, immunolocalises to stem cell niches in cartilage, promotes escape of stem cells from quiescent recycling, differentiation and attainment of pluripotency and migratory properties. These participate in tissue development and morphogenesis, ECM remodelling and repair. PPS also localises in the nucleus of stromal stem cells, promotes development of chondroprogenitor cell lineages, ECM synthesis and repair and discal repair by resident disc cells. The availability of recombinant perlecan and PPS offer new opportunities in repair biology. These multifunctional agents offer welcome new developments in repair strategies for the IVD.

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