Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role

D’Adamo, Stefania; Cetrullo, Silvia; Panichi, Veronica; Mariani, Erminia; Flamigni, Flavio; Borzı̀, Rosa Maria

doi:10.3390/cells9051232

Cited by 34 publications

(54 citation statements)

References 158 publications

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“…OA is one the most common degenerative joint diseases, and the application of phytochemicals is recommended to adjust ECM homeostasis during arthritis progression [ 20 ]. Because dietary nutraceuticals and antioxidants are generally not sufficiently effective for protection against OA development, direct administration of bioactive compounds into the knee joint capsule is a promising option [ 21 , 22 ]. Pretreatment with SMN has been shown to alleviate TNF-α-stimulated inflammatory responses in chondrocytes, and SMN has also been used in combination with NASIDs to treat OA [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Silymarin modulates catabolic cytokine expression through Sirt1 and SOX9 in human articular chondrocytes

Chen

et al. 2021

J Orthop Surg Res

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Background Silymarin (SMN), a polyphenolic flavonoid, is involved in multiple bioactive functions including anti-inflammation. Pretreatment with SMN demonstrated chondroprotection against tumour necrosis factor-alpha (TNF-α) stimulation in a chondrocyte cell line. However, pre- and posttreatment with phytochemicals have varying effects on osteoarthritis (OA) chondrocytes, and the therapeutic potential of SMN after catabolic cytokine stimulation is not fully elucidated. Methods The cytotoxicity of SMN (12.5, 25, 50 and 100 μM) was evaluated in human primary chondrocytes. The chondrocytes were supplemented with SMN (25 and 50 μM) after interleukin-1beta (IL-1β) stimulation. The mRNA expression and protein production of catabolic/anabolic cytokines as well as extracellular matrix (ECM) components were evaluated. Results High-dose SMN (100 μM) impaired the mitochondrial activity in chondrocytes, and 50 μM SMN further caused cell death in IL-1β-stimulated cells. The addition of 25 μM SMN ameliorated cell senescence; downregulated the catabolic genes of inducible nitric oxide synthase, IL-1β, TNF-α, matrix metalloproteinase-3 (MMP-3), MMP-9 and MMP-13; upregulated the anabolic genes of tissue inhibitor of metalloproteinase-1 (TIMP-1) and collagen type II alpha 1; and restored the expression of chondrogenic phenotype genes SOX9 and sirtuin-1 (Sirt1). In addition, the production of IL-1β, MMP-3 and MMP-9 decreased with an increase in TIMP-1 secretion. However, the mRNA levels of IL-6, IL-8 and IL-10 and protein production remained high. The addition of nicotinamide, a Sirt1 inhibitor, downregulated SOX9 and attenuated the therapeutic effects of SMN on IL-1β-stimulated chondrocytes. Conclusion SMN regulates the chondrocyte phenotype through Sirt1 and SOX9 to improve ECM homeostasis and may serve as a complementary therapy for early-stage knee OA.

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Section: Discussionmentioning

confidence: 99%

Silymarin modulates catabolic cytokine expression through Sirt1 and SOX9 in human articular chondrocytes

Chen

et al. 2021

J Orthop Surg Res

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“…Anthocyanins have been demonstrated to be chondroprotective, having anti-inflammatory properties and downregulating pro-inflammatory cytokines and MMPs, in both in vivo and in vitro models of previous studies 26 – 30 . However, the effect of anthocyanins on AGEs induced OA has not been extensively studied.…”

Section: Introductionmentioning

confidence: 94%

Chondroprotective effects of purple corn anthocyanins on advanced glycation end products induction through suppression of NF-κB and MAPK signaling

Chuntakaruk

Kongtawelert

Pothacharoen

2021

Sci Rep

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Formation of advanced glycation end products (AGEs), which are associated with diabetes mellitus, contributes to prominent features of osteoarthritis, i.e., inflammation-mediated destruction of articular cartilage. Among the phytochemicals which play a role in anti-inflammatory effects, anthocyanins have also been demonstrated to have anti-diabetic properties. Purple corn is a source of three major anthocyanins: cyanidin-3-O-glucoside, pelargonidin-3-O-glucoside and peonidin-3-O-glucoside. Purple corn anthocyanins have been demonstrated to be involved in the reduction of diabetes-associated inflammation, suggesting that they may have a beneficial effect on diabetes-mediated inflammation of cartilage. This investigation of the chondroprotective effects of purple corn extract on cartilage degradation found a reduction in glycosaminoglycans released from AGEs induced cartilage explants, corresponding with diminishing of uronic acid loss of the cartilage matrix. Investigation of the molecular mechanisms in human articular chondrocytes showed the anti-inflammatory effect of purple corn anthocyanins and the metabolite, protocatechuic acid (PCA) on AGEs induced human articular chondrocytes via inactivation of the NFκb and MAPK signaling pathways. This finding suggests that purple corn anthocyanins and PCA may help ameliorate AGEs mediated inflammation and diabetes-mediated cartilage degradation.

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“…The reported values represent the average of six measurements at a given pH value. Based on electrophoretic mobility values, the surface charge density (δ) was determined from the equation [1]:…”

Section: Zeta Potential Measurementsmentioning

confidence: 99%

Molecular and Cellular Effects of Chemical Chaperone—TUDCA on ER-Stressed NHAC-kn Human Articular Chondrocytes Cultured in Normoxic and Hypoxic Conditions

et al. 2021

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Osteoarthritis (OA) is considered one of the most common arthritic diseases characterized by progressive degradation and abnormal remodeling of articular cartilage. Potential therapeutics for OA aim at restoring proper chondrocyte functioning and inhibiting apoptosis. Previous studies have demonstrated that tauroursodeoxycholic acid (TUDCA) showed anti-inflammatory and anti-apoptotic activity in many models of various diseases, acting mainly via alleviation of endoplasmic reticulum (ER) stress. However, little is known about cytoprotective effects of TUDCA on chondrocyte cells. The present study was designed to evaluate potential effects of TUDCA on interleukin-1β (IL-1β) and tunicamycin (TNC)-stimulated NHAC-kn chondrocytes cultured in normoxic and hypoxic conditions. Our results showed that TUDCA alleviated ER stress in TNC-treated chondrocytes, as demonstrated by reduced CHOP expression; however, it was not effective enough to prevent apoptosis of NHAC-kn cells in either normoxia nor hypoxia. However, co-treatment with TUDCA alleviated inflammatory response induced by IL-1β, as shown by down regulation of Il-1β, Il-6, Il-8 and Cox2, and increased the expression of antioxidant enzyme Sod2. Additionally, TUDCA enhanced Col IIα expression in IL-1β- and TNC-stimulated cells, but only in normoxic conditions. Altogether, these results suggest that although TUDCA may display chondoprotective potential in ER-stressed cells, further analyses are still necessary to fully confirm its possible recommendation as potential candidate in OA therapy.

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Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role

Cited by 34 publications

References 158 publications

Silymarin modulates catabolic cytokine expression through Sirt1 and SOX9 in human articular chondrocytes

Silymarin modulates catabolic cytokine expression through Sirt1 and SOX9 in human articular chondrocytes

Chondroprotective effects of purple corn anthocyanins on advanced glycation end products induction through suppression of NF-κB and MAPK signaling

Molecular and Cellular Effects of Chemical Chaperone—TUDCA on ER-Stressed NHAC-kn Human Articular Chondrocytes Cultured in Normoxic and Hypoxic Conditions

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