Composition Analysis and Pharmacological Activity of Avocado/Soybean Unsaponifiable Products Used in the Treatment of Osteoarthritis

Objective: Avocado/soybean unsaponifiables (ASUs) are commonly used to treat OA symptoms. However, there are many ASU mixtures on the market with differing compositions and pharmacological activities. This study aimed to compare the composition and pharmacological activity of seven commercially available ASU products on human osteoarthritis chondrocytes.Methods: The contents of the lipidic part of ASUs were characterized by gas chromatography analysis using a VARIAN 3400 chromatograph. The pharmacological activity of the ASU products was tested on human osteoarthritis chondrocytes cultured in alginate beads. Their effects were evaluated on aggrecan, interleukin (IL)-6 and -8, and matrix metalloproteases (MMP)-3 using immunoassays and on nitric oxide through measurement of nitrite via spectrometry.Results: PIASCLEDINE-ExpASU® showed a specific profile with the presence of chromatographic peaks corresponding to an alkyl furan fraction and alkyl triols. PIASCLEDINE-ExpASU®, Persemax, Insaponifiable 300, Arthrocen, and Arthocare contained quantifiable amounts of tocopherol, while tocopherol was undetectable in Avovida and Saponic. Squalene was found only in PIASCLEDINE-ExpASU®. The abundance of sterols varied depending on the product. PIASCLEDINE-ExpASU® was the most active of the tested ASU products in inhibiting nitric oxide, IL-6, and IL-8 production by chondrocytes. With the exception of Saponic and Persemax, all the ASU mixtures either slightly or significantly increased aggrecan production. MMP-3 levels were significantly decreased by Insaponifiable 300 and PIASCLEDINE-ExpASU® and significantly increased by Saponic.Conclusion: The composition of PIASCLEDINE-ExpASU® is different to that of the other evaluated ASU mixtures. This specific composition explains its better pharmacological activity, including the higher inhibitory effect on pro-inflammatory and pro-catabolic factors. Our findings are helpful in providing a basis for understanding the symptomatic effect of PIASCLEDINE-ExpASU® in patients with osteoarthritis.

Synovial mesenchymal stem cell-derived exosomal miR-320c enhances chondrogenesis by targeting ADAM19

Background: Synovial mesenchymal stem cell (SMSC)-derived exosomes show treatment potential in osteoarthritis, although their functional mechanism is still unclear. Materials & methods: Osteoarthritis chondrocytes and normal SMSC were cultured. Subsequently, chondrocytes were co-cultured with SMSC or miR-320c-overexpressing SMSC-derived exosomes, or directly transfected with miR-320c mimic. Furthermore, compensate experiments were conducted. Results: SMSC promoted chondrocyte proliferation, migration, COL2A1 and ACAN expressions while suppressing apoptosis by transmitting exosomes. Furthermore, miR-320c-overexpressing SMSC-derived exosomes and direct miR-320c overexpression in chondrocytes presented more significant effect on enhancing chondrogenesis. In addition, miR-320c directly targeted ADAM19, and ADAM19 overexpression compensated the regulation of miR-320c on chondrogenesis. Conclusion: SMSC-derived exosomal miR-320c enhances chondrogenesis through targeting ADAM19, highlighting a potentially novel mechanism of SMSC in treating osteoarthritis.

5,7,3′,4′-tetramethoxyflavone ameliorates cholesterol dysregulation by mediating SIRT1/FOXO3a/ABCA1 signaling in osteoarthritis chondrocytes

Dyslipidemia has been associated with the development of osteoarthritis. Our previous study found that 5,7,3′,4′-tetramethoxyflavone (TMF) exhibited protective activities against the pathological changes of osteoarthritis. Aim: To investigate the roles of TMF in regulating ABCA1-mediated cholesterol metabolism. Methods: Knockdown and overexpression were employed to study gene functions. Protein–protein interaction was investigated by co-immunoprecipitation, and the subcellular locations of proteins were studied by immunofluorescence. Results: IL-1β decreased ABCA1 expression and induced apoptosis. Therapeutically, TMF ameliorated the effects of IL-1β. FOXO3a knockdown expression abrogated the effects of TMF, and FOXO3a overexpression increased ABCA1 expression by interacting with LXRα. TMF promoted FOXO3a nuclear translocation by activating SIRT1 expression. Conclusions: TMF ameliorates cholesterol dysregulation by increasing the expression of FOXO3a/LXRα/ABCA1 signaling through SIRT1 in C28/I2 cells.

Lycium barbarum polysaccharides in ageing and its potential use for prevention and treatment of osteoarthritis: a systematic review

Background Lycium barbarum polysaccharide (LBP), the most abundant functional component of wolfberry, is considered a potent antioxidant and an anti-ageing substance. This review aims to outline the hallmarks of ageing in the pathogenesis of osteoarthritis (OA), followed by the current understanding of the senolytic effect of LBP and its potential use in the prevention and treatment of OA. This will be discussed through the lens of molecular biology and herbal medicine. Methods A literature search was performed from inception to March 2020 using following keywords: “Lycium barbarum polysaccharide”, “DNA damage”, antioxidant, anti-apoptosis, anti-inflammation, anti-ageing, osteoarthritis, chondrocytes, fibroblasts, osteoblasts, osteoclasts, and “bone mesenchymal stem cell”. The initial search yielded 2287 papers, from which 35 studies were selected for final analysis after screening for topic relevancy by the authors. Results In literature different in vitro and in vivo ageing models are used to demonstrate LBP’s ability to reduce oxidative stress, restore mitochondrial function, mitigate DNA damage, and prevent cellular senescence. All the evidence hints that LBP theoretically attenuates senescent cell accumulation and suppresses the senescence-associated secretory phenotype as observed by the reduction in pro-inflammatory cytokines, like interleukin-1beta, and matrix-degrading enzymes, such as MMP-1 and MMP-13. However, there remains a lack of evidence on the disease-modifying effect of LBP in OA, although its chondroprotective, osteoprotective and anti-inflammatory effects were reported. Conclusion Our findings strongly support further investigations into the senolytic effect of LBP in the context of age-related OA.

Circ_0116061 regulated the proliferation, apoptosis, and inflammation of osteoarthritis chondrocytes through regulating the miR-200b-3p/SMURF2 axis

Background Circular RNA (circRNA) has been shown to be associated with osteoarthritis (OA) progression. Circ_0116061 has been found to be highly expressed in OA cartilage tissues, but its role and mechanism in OA progression remain unclear. Methods Expression levels of circ_0116061, microRNA (miR)-200b-5p, and Smad ubiquitin regulatory factor 2 (SMURF2) were detected using quantitative real-time PCR. The proliferation and apoptosis of cells were measured using cell counting kit 8 (CCK8) assay, colony formation assay, and flow cytometry. Furthermore, the protein levels of proliferation-related marker, apoptosis-related markers, inflammatory factors, and SMURF2 were tested using western blot (WB) analysis. In addition, the interaction between miR-200b-3p and circ_0116061 or SMURF2 was examined using dual-luciferase reporter assay and biotin-labeled RNA pull-down assay. Results Circ_0116061 and SMURF2 were highly expressed, and miR-200b-3p was lowly expressed in OA cartilage tissues. Knockdown of circ_0116061 could promote the proliferation and inhibit the apoptosis and inflammation of OA chondrocytes. MiR-200b-3p could be sponged by circ_0116061, and its inhibitor could reverse the regulation of circ_0116061 silencing on the biological functions of OA chondrocytes. SMURF2 was a target of miR-200b-3p, and its expression was positively regulated by circ_0116061. Silencing of SMURF2 also could enhance the proliferation and suppress the apoptosis and inflammation of OA chondrocytes. Furthermore, the regulation of circ_0116061 silencing on the biological functions of OA chondrocytes also could be reversed by SMURF2 overexpression. Conclusion Our data showed that circ_0116061 might regulate the miR-200b-3p/SMURF2 axis to promote the progression of OA.