Attenuation of inflammation and cartilage degradation by sulfasalazine-containing hyaluronic acid on osteoarthritis rat model

Epidemiologic and etiologic approach of osteoarthritis

061 ALTERED SCLEROSTIN SYNTHESIS IN CARTILAGE AND BONE CONTRIBUTE OA PATHOLOGY

To explore the involvement of synovial macrophages in early cartilage damage in osteoarthritis (OA), and to identify the role of matrix metalloproteinase 3 (MMP-3) in the pathology of early and late OA. The role of synovial macrophages in MMP-mediated damage in OA was studied by depleting synovial macrophages prior to elicitation of a collagenase-induced instability model of OA. The expression of MMP in synovium and cartilage was monitored using TaqMan analysis. In spontaneous and induced OA, cartilage pathology was scored in MMP-3-knockout mice and control mice, by histologic assessment and VDIPEN staining. On day 14 following induction of OA, MMP-mediated neoepitopes were detected in cartilage from mice with mild experimental OA (mean +/- SD positively stained surface area 20 +/- 3.2%). Remarkably, by depleting synovial macrophages prior to induction of OA, the generation of MMP-induced neoepitopes was largely prevented (mean +/- SD positively stained surface area 5 +/- 1%; P< 0.001), indicating an important role for synovial macrophages in the occurrence of MMP-mediated cartilage damage. We observed a strong decrease in MMP-3 and MMP-9 expression in synovial but not cartilage tissue in macrophage-depleted joints. Among 2-year-old mice, spontaneous OA-like changes in the lining layer were significantly decreased in MMP-3-knockout mice compared with control mice. Even more striking was the 67% reduction in the occurrence of severe cartilage damage in MMP-3-knockout mice. In addition, MMP-mediated VDIPEN expression was significantly decreased, indicating reduced MMP-mediated cartilage breakdown. The results of this study prove that MMP-3 is involved in the generation of severe cartilage damage in murine OA. Synovial macrophages are crucial in early MMP activity and appear to mediate MMP production in synovium rather than cartilage.

Synovial Mesenchymal Stem Cell-Derived EV-Packaged miR-31 Downregulates Histone Demethylase KDM2A to Prevent Knee Osteoarthritis

Improving subchondral bone integrity reduces progression of cartilage damage in experimental osteoarthritis preceded by osteoporosis

Ultrastructural change of the subchondral bone increases the severity of cartilage damage in osteoporotic osteoarthritis of the knee in rabbits

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, subchondral bone erosion, and chronic inflammation. Current treatments primarily focus on symptom relief and have significant side effects, highlighting the need for safer, more effective alternatives. Cissus quadrangularis extract (CQE), containing bioactive flavonoids quercetin and isorhamnetin, has shown potential anti-inflammatory and cartilage-protective properties. This study aimed to investigate the anti-osteoarthritic effects and mechanisms of action of CQE in a monosodium iodoacetate (MIA)-induced OA rat model. Sprague-Dawley (SD) rats were induced with OA through intra-articular injection of MIA and treated with CQE at doses of 30, 50, and 100 mg/kg body weight (BW)/day. The effects of CQE on knee joint damage, subchondral bone erosion, cartilage structure, proteoglycan content, and the expression of inflammatory mediators and matrix metalloproteinases (MMPs) were assessed using micro-computed tomography (micro-CT), histological staining, immunofluorescence, and real-time reverse transcription-polymerase chain reaction (RT-PCR). CQE significantly mitigated knee joint damage, reduced subchondral bone erosion, and enhanced bone volume and trabecular structure in MIA-induced OA rats. It also preserved cartilage integrity by maintaining proteoglycan content and the expression of collagen type II alpha 1 (COL2A1) and aggrecan. Moreover, CQE suppressed the mRNA expression of inflammatory mediators [inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX)], pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α)], and MMPs (MMP-2, MMP-3, MMP-9, and MMP-13), indicating strong anti-inflammatory and cartilage-protective effects. CQE exhibits significant therapeutic potential in managing OA by targeting multiple aspects of disease progression, including inflammation, cartilage degradation, and bone erosion. Further research is needed to explore long-term efficacy, safety, and the molecular mechanisms of CQE, as well as to validate these findings in human clinical trials.

In this study, we investigated the relationship between anti-inflammatory mechanisms and the combined ameliorating effects of rose hip powder (RHP) and green tea seed extract (GTSE) in a monosodium iodoacetate (MIA)-induced osteoarthritis (OA) animal model. We confirmed the individual effects of RHP (500 mg/kg bw) and GTSE (50 mg/kg bw) in the OA model. Treatment with the mixture of RHP and GTSE (Mix) resulted in significantly enhanced stance and propulsion times compared to treatment with RHP or GTSE alone. To examine the combined effects of RHP and GTSE in vivo, pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were measured. The administration of Mix significantly reduced the expression of pro-inflammatory cytokines. Additionally, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions were attenuated to a greater extent after the administration of Mix compared to the other treatments. Furthermore, we evaluated the anti-osteoarthritic effects of RHP, GTSE, and Mix on articular cartilage damage using micro-computed tomography (micro-CT) in OA in rats. After three weeks of treatment, we observed that the administration of RHP, GTSE, and Mix protected against bone destruction and reduced the number of erosion lacunae, but there was no statistical difference among RHP, GTSE, and Mix. Although additional research is warranted, our results suggest that the biological effects of GTSE were enhanced by RHP supplementation to include anti-inflammatory effects, with the potential ability of offering a benefit to OA patients.

BackgroundArticular cartilage damage in osteoarthritis (OA) is characterized by degeneration of the extracellular matrix. Matrix metalloproteinases (MMPs) play a crucial role in the modulations of cell-matrix interactions and degradation of...

Lilium lancifolium (LL) is widely cultivated in East Asia and used to attenuate airway diseases. Our current study aimed to investigate the therapeutic effect of LL on pain level and inflammatory response in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). We first examined the effect of LL on inflammatory cytokines and inflammatory mediators in IL-1β-treated HTB-94 cells. The LL extract was found to significantly inhibit the levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), and prostaglandin-E2 (PGE-2) in Interleukin-1 β (IL-1β)-stimulated HTB-94 cells in a dose-dependent manner. Moreover, chronic oral administration of LL effectively restored the weight-bearing distribution in the rat model of MIA-induced OA. In addition, administration of LL inhibited inflammatory cytokines and inflammatory mediators, such as C-reactive protein (CRP), IL-6, leukotriene B4 (LTB-4), PGE-2, and matrix metalloproteinase-9 (MMP-9). Our findings collectively suggested LL as one of the potential therapeutic agents for OA, owing to its properties of reducing pain and inflammatory responses.

BACKGROUND/OBJECTIVESSteamed ginger extract (GGE03) has been proposed as a complementary treatment for osteoarthritis (OA). On the other hand, the efficacy and mechanism are incompletely understood. This study examined the anti-osteoarthritic effects of GGE03 in monosodium iodoacetate (MIA)-induced OA Sprague-Dawley (SD) rats.MATERIALS/METHODSThe rats were divided into the following groups: normal control group (NC); OA control group (OC); OA+30, 50, or 100 mg/kg body weight (BW)/day GGE03 group (O+G30, O+G50, or O+G100); OA+150 mg/kg BW/day methyl sulfonyl methane (MSM, positive control group (O+M). The SD rats were given GGE03 or MSM orally for 5 weeks. MIA was injected intra-articularly into the knee joints on day 15 to induce OA. The exercise performance test, pain behavior test, micro-computed tomography, histological examination, and immunofluorescence staining were performed on the knee joint. The inflammatory mediators, cytokines, and matrix metalloproteinase (MMP) mRNA expression were measured in the knee joint synovial fluid.RESULTSThe OC group had significantly shorter exercise times to exhaustion and withdrawal threshold according to the von Frey test, more severe knee joint swelling and subchondral bone erosion than the NC group, and reduced type II collagen and aggrecan expression in the articular cartilage. The OC group showed a significantly higher mRNA expression of inflammatory mediators, cytokines, and MMPs than the NC group. In OA rats, GGE03 administration reduced knee swelling and cartilage degradation and increased type II collagen and aggrecan expression in the articular cartilage. GGE03 administration reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, MMP-2, MMP-3, MMP-9, and MMP-13 in the synovia of the knee joints.CONCLUSIONGGE03 administration is a useful supplementary agent for anti-OA treatment.

Purpose: To investigate the effect of benzoxime on degradation of articular cartilage in a rat model of osteoarthritis (OA), and the mechanism involved.Methods: The OA rat model was prepared by injecting monosodium iodoacetate (MIA) intra-articularly to Wistar rats. Rats in the treatment group were given benzoxime (5 mg/kg) daily for 21 days through the intra-articular route. The animals were then examined for behavioral changes by assessment of asymmetry in bearing weight and paw withdrawal threshold of the hind limb. Western blot assay was used for the analysis of inflammatory cytokine expressions.Results: The expression of P2X purinoceptor 7 receptor (P2X7R) mRNA was significantly elevated in the OA rats (p &lt; 0.02). However, benzoxime treatment caused a marked decrease in the level of P2X1-8R mRNA. Benzoxime treatment also prevented asymmetry in bearing weight, decreased paw withdrawal threshold, and inhibited the expressions of interleukin-1β, interleukin-6 and tumor necrosis factor-α in plasma and cartilage. Moreover, benzoxime exhibited significant inhibitory effects on the expressions of P2X7R, matrix metalloproteinase (MMP)-13 and prostaglandin E2 (PGE2) in cartilage tissue. It also significantly suppressed OA-induced increases in the levels of inhibitor of nuclear factor-κB (NF-κB) kinase (IKK)α, IKKβ, IκBα and NF-κB p65, and blocked OA-induced increases in the expressions of P2X7R, MMP-13 and PGE2.Conclusion: These results demonstrate that benzoxime prevents cartilage degradation in OA rats by targeting NF-κB signaling pathway. Thus, benzoxime possesses clinical and therapeutic potentials for the prevention of cartilage degradation in OA.Keywords: Interleukin-1β, Purinoceptor-7, Benzoxime, Osteoarthritis, Prostaglandin, Matrix metalloproteinases

Osteoarthritis is a widespread chronic degenerative disease marked by the deterioration of articular cartilage, modifications in subchondral bone, and a spectrum of symptoms, including pain, stiffness, and disability. Ultimately, this condition impairs the patient’s quality of life. This study aimed to evaluate the therapeutic efficacy of standardized Boswellia serrata gum resin extract (BSRE) in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. A total of 60 rats were allocated into six groups: normal control group (NC), osteoarthritis control (injected with MIA, OC), O + B50 (injected with MIA and treated with 50 mg/kg body weight (BW) BSRE), O + B75 (injected with MIA and treated with 75 mg/kg BW BSRE), O + B100 (injected with MIA and treated with 100 mg/kg BW BSRE), and O + M (injected with MIA and treated with 150 mg/kg BW methyl sulfonyl methane). Several parameters, including knee joint swelling, histopathological changes, and the expression of collagen type II alpha 1 (COL2A1) and aggrecan, were comprehensively assessed. Concurrently, the serum levels and mRNA expression of inflammatory mediators, cytokines, and matrix metalloproteinases (MMPs) were analyzed in both the serum and knee joint synovium. The results demonstrated that BSRE significantly mitigated knee joint swelling, cartilage destruction, and tissue deformation. Notably, BSRE administration markedly upregulated the expression of COL2A1 and aggrecan while concurrently reducing levels of nitric oxide, prostaglandin E2, leukotriene B4, interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Furthermore, a substantial decrease was observed in the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, IL-6, TNF-α and MMP-3 and -13, thereby indicating promising therapeutic implications for osteoarthritis. In conclusion, BSRE exhibited anti-inflammatory properties and inhibited cartilage matrix degradation in a rat model of MIA-induced osteoarthritis, with the O + B100 group showing significant reductions in swelling and notable improvements in joint cartilage damage. These findings illuminate the preventive and therapeutic potential of BSRE for osteoarthritis treatment, emphasizing the criticality of exhaustive evaluation of novel compounds.

Adenovirus-mediated transduction with Histone Deacetylase 4 ameliorates disease progression in an osteoarthritis rat model

BACKGROUNDS/OBJECTIVESThis study examined the anti-osteoarthritic effects of a Curcuma longa Linn ethanol extract (CLE), standardized to 500 mg/g of curcuminoids, in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) Sprague-Dawley (SD) rats.MATERIALS/METHODSThe rats were divided into a normal control group (NC), OA control group (OC), OA +10, 20, 30, or 50 mg/kg body weight (BW)/day CLE-administered group (O+CL10, O+CL20, O+CL30, or O+CL50), and OA+150 mg/kg BW/day methyl sulfonyl methane (MSM, positive control)-administered group (O+M). The rats were given oral doses of CLE or MSM for 5 weeks, with an intra-articular injection of MIA into their knee joints on the 15th day to induce OA. Micro-computed tomography, histological examination, and immunofluorescence staining were performed on the knee joint. The inflammatory mediators, cytokines, and matrix metalloproteinase (MMP) mRNA expression were measured in the knee joint synovial fluid.RESULTSThe OC group showed more severe knee joint swelling and subchondral bone erosion than the NC group, and aggrecan and type II collagen expression in the articular cartilage was reduced. The OC group exhibited lower mRNA expression of inflammatory mediators, cytokines, and MMPs than the NC group. In OA-induced rats, the oral administration of the CLE reduced knee swelling and cartilage degradation and increased aggrecan and type II collagen expression in the articular cartilage. CLE administration reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, MMP-2, MMP-3, MMP-9, and MMP-13 in the synovia of knee joints. In particular, these levels reached the same as the positive control group, the O+M group.CONCLUSIONThe CLE had potent anti-OA effects in MIA-induced OA rats by suppressing the expression of inflammatory mediators, cytokines, and MMPs, alleviating cartilage degradation. Hence, the CLE is a potential functional food ingredient that can prevent and improve OA.