Pyrroloquinoline Quinone Slows Down the Progression of Osteoarthritis by Inhibiting Nitric Oxide Production and Metalloproteinase Synthesis

Abstract

Osteoarthritis (OA) is the most common arthritis and also one of the major causes of joint pain in elderly people. The aim of this study was to investigate the effects of pyrroloquinoline quinone (PQQ) on degenerated-related changes in osteoarthritis (OA). SW1353 cells were stimulated with IL-1β to establish the chondrocyte injury model in vitro. PQQ was administrated into SW1353 cultures 1 h before IL-1β treatment. Amounts of MMP-1, MMP-13, P65, IκBα, ERK, p-ERK, P38, and p-P38 were measured via western blot. The production of NO was determined by Griess reaction assay and reflected by the iNOS level. Meniscal-ligamentous injury (MLI) was performed on 8-week-old rats to establish the OA rat model. PQQ was injected intraperitoneally 3 days before MLI and consecutively until harvest, and the arthritis cartilage degeneration level was assessed. The expressions of MMP-1 and MMP-13 were significantly downregulated after PQQ treatment compared with that in IL-1β alone group. NO production and iNOS expression were decreased by PQQ treatment compared with control group. Amounts of nucleus P65 were upregulated in SW1353 after stimulated with IL-1β, while PQQ significantly inhibited the translocation. In rat OA model, treatment with PQQ markedly decelerated the degeneration of articular cartilage. These findings suggested that PQQ could inhibit OA-related catabolic proteins MMPs expression, NO production, and thus, slow down the articular cartilage degeneration and OA progression. Owing to its beneficial effects, PQQ is expected to be a novel pharmacological application in OA clinical prevention and treatment in the near future.

Early PQQ supplementation has persistent long‐term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice

“…IL‐6 production was also significantly diminished by PQQ treatment in synovio‐cytes, via attenuating phosphorylation of p38 and JNK (55). In addition, an in vivo model of osteoarthritis has demonstrated an effect of PQQ in decelerating inflammatory responses via inhibition of NO production by suppressing I k Bα degradation (56), suggesting PQQ acts systemically to modulate IL‐6 and NO levels through different pathways. Notably, the ceramide content in livers of WD‐fed weanling mice was lowered by PQQ, suggesting that the disease‐causing effects of excess lip‐ids on inflammation and oxidative stress had already been mitigated in early life.…”

Silencing of Wnt5a prevents interleukin-1β-induced collagen type II degradation in rat chondrocytes

“…The chondrocytes of passage 2 were cultivated with serum-free DMEM for 24 h, and stimulated with medium containing 10 ng/ml IL-1β for 0, 1, 6, 12 or 24 h, respectively, as previously described (22). …”

The Life History of Pyrroloquinoline Quinone (PQQ): A Versatile Molecule with Novel Impacts on Living Systems

“…The bacterial isolates synthesizing PQQ have higher tolerance to ultraviolet C radiation and high tolerance to DNA damage when grown in the absence of inorganic phosphate (PO 4 3− ), [163]. The Herbaspirillum seropedica (gram negative) genome codes for GDH and Erwinia herbicolaencodes pqqE secreting minute molar PQQ levels to attain greater GDH activity for gluconic acid (33.46 mM) hyper-secretion [164].…”

“…PQQ has a coplanar tryptophan and a disulphide ring as its active site residual location, hence structure is derived from adjacent cysteine residues requiring Ca 2+ for activity and uses cytochrome c L as its electron acceptor [80][81][82][83][84]. m-GDH in Escherichia coli have molecular structure and catalytic reaction site, N-terminal domain to anchor the domain in periplasmic t and activity shown by X-ray modeled structure of the α-subunit in PQQ active site [161][162][163][164][165]. The m-GDH of E.coli is a securely fixed with ubiquinone localized coenzyeme (PQQ) [120].…”