Raymond Purves Bone and Joint Research Laboratories, Faculty of Health and Science, Institute of Bone and Joint Research, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, Australia.
Bioimaging Research Hub, Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom.
Stem Cells Dev. 2022 Aug;31(15-16):406-430. doi: 10.1089/scd.2022.0007. Epub 2022 Mar 14.
This review highlights the attributes of pentosan polysulfate (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 signaling pathways similar to those operative in the development of OA in articular cartilage. PPS acts as a heparan sulfate (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 sulfate (CS) hybrid proteoglycan (HSPG2/perlecan), that have important matrix-stabilizing 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 and expansion of cartilaginous rudiments, and has roles in matrix stabilization and repair. Perlecan is a perinuclear and nuclear proteoglycan (PG) in IVD cells with roles in chromatin organization and control of transcription factor activity, immunolocalizes 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 remodeling and repair. PPS also localizes 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 offers new opportunities in repair biology. These multifunctional agents offer welcome new developments in repair strategies for the IVD.
这篇综述强调了聚戊糖多硫酸酯（PPS）在促进椎间盘（IVD）修复过程中的特性。PPS 已被归类为一种治疗骨关节炎的药物（DMOAD），许多研究表明其在对抗骨关节炎（OA）发生时软骨组织退行性变化方面具有积极作用。IVD 的退行性变化也涉及炎症细胞因子、降解蛋白酶和细胞信号通路，这些与关节软骨中 OA 的发展相似。PPS 作为硫酸乙酰肝素（HS）类似物发挥作用，对软骨产生有益影响。IVD 含有小细胞膜 HS 蛋白聚糖（HSPG），如连接蛋白、聚糖蛋白和大型多功能 HS/软骨素硫酸盐（CS）杂合蛋白聚糖（HSPG2/ 蛋白聚糖），具有重要的基质稳定特性，并隔离、控制和呈现来自 FGF、VEGF、PDGF 和 BMP 家族的生长因子，以促进细胞增殖、分化和基质合成。HSPG2 还具有软骨生成特性，刺激细胞外基质（ECM）成分的合成和软骨原基的扩张，并在基质稳定和修复中发挥作用。蛋白聚糖 2 是 IVD 细胞中的核周和核蛋白聚糖（PG），具有染色质组织和转录因子活性控制的作用，免疫定位在软骨中的干细胞巢，促进干细胞从静止循环、分化和获得多能性和迁移特性中逃逸。这些参与组织发育和形态发生、ECM 重塑和修复。PPS 还定位于基质干细胞的核内，促进软骨祖细胞谱系的发育、ECM 合成和修复以及驻留椎间盘细胞的椎间盘修复。重组蛋白聚糖 2 和 PPS 的可用性为修复生物学提供了新的机会。这些多功能药物为 IVD 的修复策略提供了受欢迎的新发展。
