Efficacy of Chondroitin Sulfate for Painful Knee Osteoarthritis: A One-Year, Randomized, Double-Blind, Multicenter Clinical Study in Japan

Abstract

We explored the effects of chondroitin sulfate on knee osteoarthritis in a one-year, randomized, doubleblind, dose-comparison study. Patients with painful, Kellgren-Lawrence grade 2-3, osteoarthritis of the knee were treated with oral chondroitin sulfate at a dose of either 260 mg/d (low-dose group, control group) or 1560 mg/d (high-dose group). Symptoms were evaluated by the Lequesne's index and visual analog scale for pain. We made subgroup analyses according to background symptom severity (Lequesne's index ≥8 or <8) in 73 patients. Serum level of cartilage oligomeric matrix protein and hyaluronic acid were also determined. In the subgroup with severe symptoms (Lequesne's index ≥8), the chondroitin sulfate dose of 1560 mg/d improved pain faster after 6 and 9 months' therapy. However, no dose-related effects were found on cartilage oligomeric matrix protein or hyaluronic acid levels. Chondroitin sulfate also had good tolerability. We conclude that chondroitin sulfate is useful for pain control in knee osteoarthritis.Key words chondroitin sulfate; pain-management; clinical trial; randomized controlled trial Osteoarthritis (OA) is the most common form of arthritis and is a major cause of morbidity, activity limitation, physical disability, excess health care utilization, and reduced healthrelated QOL, especially in people aged 65 years and older.

The Function of PPARγ/AMPK/SIRT-1 Pathway in Inflammatory Response of Human Articular Chondrocytes Stimulated by Advanced Glycation End Products

“…SIRT-1 inactivates NF-κB by deacetylating the p65 subunit, 54) and in OA, inactivation of NF-κB inhibits the AGEs-induced inflammatory response in chondrocytes. 36) Furthermore, pre-treatment with the AMPK agonist restored SIRT-1 levels in the AGE-treated chondrocytes.…”

“…This is consistent with a previous study showing that AGEs drive OA by enhancing the inflammatory response in the articular chondrocytes. 36) Recent studies indicate a pivotal role of the energy homeostasis regulator AMPK in the inflammatory response. Ovalbumin-induced eosinophil infiltration is more severe in the AMPK knockout mice, 45) and overexpression of constitutivelyactivated AMPK in the murine macrophages significantly inhibited inflammatory response, while AMPK inactivation had the opposite effect.…”

“…We showed an anti-inflammatory role of pioglitazone in chondrocytes, wherein it reduced the levels of TNF-α and IL-1β in the AGE-treated chondrocytes in a concentrationdependent manner. 36) Moreover, it is reported that AMPK and SIRT-1 could be regulated by PPARγ in ethanol-fed mice and TNF-α-treated hNSCs. 33,34) Therefore, we further speculated that pioglitazone can restore the p-AMPK and the SIRT-1 protein levels which were downregulated by AGEs.…”

“…In our previous study, we found that pioglitazone reduced the AGEs-triggered high levels of IL-1β and TNF-α in chondrocytes in a concentration-dependent manner. 36) Based on these findings, we hypothesized that AGEs increase the levels of pro-inflammatory factors in the cartilage chondrocytes by inhibiting PPARγ/AMPK/SIRT-1.…”

Oral glucosamine and chondroitin sulfate on synovial fluid biomarkers from osteoarthritic equine joints

“…CS and GlcN are currently recommended for humans as a "SYSADOA" -Symptomatic Slow-Acting Drug for the treatment of OA. It means that they provide pain relief and increased joint mobility only after a relatively long period of regular administration (1-2 months), and their effects last long after the end of treatment (6-9 months) (MORITA et al, 2018).…”