Protective role of Achyranthes bidentata polysaccharides against chondrocyte extracellular matrix degeneration through lncRNA GAS5 in osteoarthritis

Abstract

Achyranthes bidentata polysaccharides (ABPS) is an active ingredient of the flowering plant Achyranthes bidentata that has been previously reported to be effective for the treatment of osteoarthritis (OA). However, the underlying molecular mechanism remain to be fully clarified. Emerging studies have shown that the long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) is involved in the pathogenesis of OA. Therefore, the present study aimed to investigate the potential mechanism of ABPS by focusing on its effects on the regulation of chondrocyte extracellular matrix (ECM) homeostasis, with particular emphasis on lncRNA GAS5. In the present study, the modified Hulth method was used to construct OA rats, which were gavaged with 400 mg/kg ABPS for 8 weeks. Histopathological changes in cartilage and subchondral bone were evaluated by hematoxylin-eosin staining and Safranin O-fast green staining. In in vitro experiments, IL-1β-treated chondrocytes were infected with Lenti-lncRNA GAS5. Fluorescence in situ hybridization assay was performed to measure the expression of the lncRNA GAS5 in chondrocytes. Moreover, the relative expression level of lncRNA GAS5 in cartilage tissue and chondrocytes was detected using reverse transcription-quantitative PCR. Western blot analysis was used to detect protein expression levels of MMP-9, MMP-13, TIMP-1, TIMP-3 and type II collagen in cartilage tissue and chondrocytes. The results indicated that ABPS delayed the degradation of the ECM by chondrocytes in addition to reducing lncRNA GAS5 expression both in vivo and in vitro. Furthermore, silencing of lncRNA GAS5 expression in IL-1β-treated chondrocytes downregulated the protein expression of MMP-9 and MMP-13 whilst upregulating the expression of tissue inhibitor matrix metalloproteinase (TIMP)-1, TIMP-3 and type II collagen. To conclude, the present study provides evidence that ABPS can inhibit the expression of lncRNA GAS5 in chondrocytes to regulate the homeostasis of ECM, which in turn may delay the occurrence of cartilage degeneration during OA.

Research Progress on the Pathogenesis of Knee Osteoarthritis

“…A large number of studies have found that the intervention of specific LncRNA has an inhibitory effect on the development of osteoarthritis. For example, Achyranthes bidentata polysaccharide (ABP) can slow down the degradation of ECM by regulating the expression of lncRNA GAS5 77 . It can also inhibit thapsigargin (TG)‐induced chondrocyte endoplasmic reticulum stress (ERS) 78 through the lncRNA NEAT1/miR‐377‐3p axis to protect osteoarthritis.…”

“…For example, Achyranthes bidentata polysaccharide (ABP) can slow down the degradation of ECM by regulating the expression of lncRNA GAS5. 77 It can also inhibit thapsigargin (TG)‐induced chondrocyte endoplasmic reticulum stress (ERS) 78 through the lncRNA NEAT1/miR‐377‐3p axis to protect osteoarthritis. In conclusion, lncRNA plays an important role in regulating gene expression, maintaining cartilage and synovial cell phenotype, and stabilizing the intra‐articular environment.…”

Natural anti‐inflammatory products for osteoarthritis: From molecular mechanism to drug delivery systems and clinical trials

“…Achyranthes bidentata polysaccharides (ABPS) are a group of main bioactive components of Achyranthes (He et al, 2017). At the level of the microenvironment, ABPS regulates ECM homeostasis via inhibition of the lncRNA GAS5 and MMP-13 as well as the upregulation of TIMP-1 (Fu, Qiu, Huang, Mei, et al, 2022). At the level of cell phenotype and subcellular organelles, as known, studies of other NAIPs on chondrocytes have demonstrated that Wnt/β-catenin signaling pathway inhibition obviously suppresses OA inflammation (Zeng et al, 2014).…”

“…In a rat model of OA, BBR T A B L E 5 Polysaccharides. Regulates ECM homeostasis (Fu, Qiu, Huang, Mei, et al, 2022) Upregulation of TIMP-1. Actives the Wnt/β-catenin signaling pathway.…”

“…Promote proliferation of chondrocyte. Suppresses ER stress-induced chondrocyte apoptosis Fu, Qiu, Huang, Mei, et al, 2022;Weng et al, 2014) Abbreviations: ECM, extracellular matrix; ER, endoplasmic reticulum; MMP, matrix metalloproteinase; NAIP, natural anti-inflammatory product.…”