Monoiodoacetate-induced Osteoarthritis Research Articles

Validity evaluation of a rat model of monoiodoacetate-induced osteoarthritis with clinically effective drugs

BackgroundKnee osteoarthritis (KOA) is the most common type of joint disease in elderly people and is characterized by pain and dysfunction. Although the monoiodoacetate (MIA)-induced model is widely used as a rodent KOA model, it is important to acknowledge the inherent limitations of this model, as the MIA model develops complex pathological phases on a daily basis. An accurate understanding of this model and the selection of an appropriate time point according to the target for drug candidates can lead to the development of clinically effective drugs.MethodsChanges in the pathological state of the MIA model were assessed via histopathological evaluation. Clodronate, a bisphosphonate, and diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), were selected as models of clinically effective drugs due to their different mechanisms of action. The analgesic effects of both drugs on the MIA model were evaluated. The long-term effect of clodronate on subchondral bone osteoclasts was also evaluated.ResultsHistopathological evaluation revealed that MIA-induced symptomatic behavior occurred in the early and late phases and was accompanied by synovial inflammation and osteoclast-related joint degeneration, respectively. Although clodronate inhibited symptomatic behavior and prevented cartilage degeneration from the early to late phases, diclofenac inhibited symptomatic behavior only in the early phase. Clodronate acted locally and inhibited the activation of subchondral osteoclasts.ConclusionsPathological changes, such as synovial changes in the early phase and knee joint degeneration in the late phase, in the MIA model are similar to those in human KOA. Our results indicate that the early phase in the MIA model is appropriate for evaluating the effects of anti-inflammatory agents such as NSAIDs and corticosteroids. The late phase in the MIA model is appropriate for evaluating the effects of drugs that act on cartilage and subchondral bone.

Model of Monoiodoacetate-Induced Osteoarthritis in Laboratory Animals

Model of Monoiodoacetate-Induced Osteoarthritis in Laboratory Animals

Comparison of effects of intra-articular diclofenac etalhyaluronate and hyaluronic acid in a monoiodoacetate rat osteoarthritis model.

Diclofenac etalhyaluronate (DF-HA) sustained diclofenac release with the effects of hyaluronic acid (HA), offering long-term analgesia in osteoarthritis. In this study, the effects of DF-HA on pain improvement and osteoarthritis were evaluated in a rat knee monoiodoacetate-induced osteoarthritis model compared to HA. Eight rats per group had been injected with monoiodoacetate (2.0 mg) or saline in the right knee for 4 weeks and were injected with either DF-HA (1.25 mg/kg; 0.5 mg), HA (0.5 mg), vehicle which was a substrate without DF-HA (50 μL), or saline and followed for 4 weeks. Mechanical plantar skin sensitivity was assessed weekly using the von Frey assay. Osteoarthritis changes were monitored with Larsen scores via CT imaging at every 2 weeks. The articular cartilage was analyzed using OARSI scores through H&E, Safranin-O staining at 8 weeks. The percentage of Iba-1 positive microglia in the spinal dorsal horn and of FG + CGRP-labeled cells among FG-positive cells in the dorsal root ganglion were evaluated by immunohistochemical staining. TNF-α and IL-6 mRNA expression levels in the knee synovium were evaluated by PCR. The DF-HA showed significantly improved pain hypersensitivity compared with the HA at 6-8 weeks. The percentage of Iba-1-positive microglia was significantly lower than that in the vehicle and the percentage of FG + CGRP/FG was significantly lower than that in the HA. OARSI scores did not differ among treatment groups, Larsen scores indicated lower in the DF-HA than in the vehicle. DF-HA was as effective as HA in joint protection and significantly improved inflammatory pain compared to HA.

Novel multitarget analgesic candidate SZV-1287 demonstrates potential disease-modifying effects in the monoiodoacetate-induced osteoarthritis mouse model.

Monoiodoacetate (MIA)-induced osteoarthritis (OA) is the most commonly used rodent model for testing anti-OA drug candidates. Herein, we investigated the effects of our patented multitarget drug candidate SZV-1287 (3-(4,5-diphenyl-1,3-oxazol-2-yl) propanal oxime) that is currently under clinical development for neuropathic pain and characterized the mouse model through complex functional, in vivo imaging, and morphological techniques. Knee OA was induced by intraarticular MIA injection (0.5 and 0.8mg). Spontaneous pain was assessed based on weight distribution, referred pain by paw mechanonociception (esthesiometry), edema by caliper, neutrophil myeloperoxidase activity by luminescence, matrix metalloproteinase activity, vascular leakage and bone remodeling by fluorescence imaging, bone morphology by micro-CT, histopathological alterations by semiquantitative scoring, and glia activation by immunohistochemistry. Then, SZV-1287 (20mg/kg/day) or its vehicle was injected intraperitoneally over a 21-day period. MIA induced remarkably decreased thresholds of weight bearing and paw withdrawal, alterations in the tibial and femoral structures (reactive sclerosis, increased trabeculation, and cortical erosions), histopathological damage (disorganized cartilage structure, hypocellularity, decreased matrix staining and tidemark integrity, and increased synovial hyperplasia and osteophyte formation), and changes in the astrocyte and microglia density in the lumbar spinal cord. There were no major differences between the two MIA doses in most outcome measures. SZV-1287 inhibited MIA-induced weight bearing reduction, hyperalgesia, edema, myeloperoxidase activity, histopathological damage, and astrocyte and microglia density. SZV-1287 may have disease-modifying potential through analgesic, anti-inflammatory, and chondroprotective effects. The MIA mouse model is valuable for investigating OA-related mechanisms and testing compounds in mice at an optimal dose of 0.5mg.

Vortioxetine attenuates pain hypersensitivity in female rats with monoiodoacetate-induced osteoarthritis: role of nerve growth factor

Vortioxetine attenuates pain hypersensitivity in female rats with monoiodoacetate-induced osteoarthritis: role of nerve growth factor

NLRP3 inflammasome activation in sensory neurons promotes chronic inflammatory and osteoarthritis pain.

Pain is one of the most debilitating symptoms in rheumatic diseases. Pain often persists after total knee replacement in osteoarthritis, or when inflammation is minimal/absent in rheumatoid arthritis. This suggests that pain transitions to a chronic state independent of the original damage/inflammation. Mitochondrial dysfunction in the nervous system promotes chronic pain and is linked to NLRP3 inflammasome activation. Therefore, we investigated the role of mitochondrial dysfunction and NLRP3 inflammasome activation in the transition from acute to persistent inflammation-induced nociplastic pain and in persistent monoiodoacetate-induced osteoarthritis pain. Intraplantar injection of carrageenan in mice induced transient inflammatory pain that resolved within 7 days. A subsequent intraplantar PGE2 injection induced persistent mechanical hypersensitivity, while in naive mice it resolved within one day. Thus, this initial transient inflammation induced maladaptive nociceptor neuroplasticity, so-called hyperalgesic priming. At Day 7, when mice were primed, expression of NLRP3 inflammasome pathway components was increased, and dorsal root ganglia (DRG) neurons displayed signs of activated NLRP3 inflammasome. Inhibition of NLRP3 inflammasome with MCC950 prevented the transition from acute to chronic pain in this hyperalgesic priming model. In mice with persistent monoiodoacetate-induced osteoarthritis pain, DRG neurons displayed signs of mitochondrial oxidative stress and NLRP3 inflammasome activation. Blocking NLRP3 inflammasome activity attenuated established osteoarthritis pain. In males, NLPR3 inhibition had longer-lasting effects than in females. Overall, these data suggest that NLRP3 inflammasome activation in sensory neurons, potentially caused by neuronal oxidative stress, promotes development of persistent inflammatory and osteoarthritis pain. Therefore, targeting NLRP3 inflammasome pathway may be a promising approach to treat chronic pain.

Assessment of the Efficacy of Bone Marrow-Derived Mesenchymal Stem Cells against a Monoiodoacetate-Induced Osteoarthritis Model in Wistar Rats.

Osteoarthritis (OA) of the knee is a debilitating condition that can severely limit an individual's mobility and quality of life. This study was designed to evaluate the efficacy of bone marrow-derived mesenchymal stem cell (BM-MSC) treatment in cartilage repair using a rat model of monoiodoacetate- (MIA-) induced knee OA. OA was induced in the knee joint of rats by an intracapsular injection of MIA (2 mg/50 μL) on day zero. The rats were divided into three groups (n = 6): a normal control group, an osteoarthritic control group, and an osteoarthritic group receiving a single intra-articular injection of BM-MSCs (5 × 106 cells/rat). The knee diameter was recorded once per week. By the end of the performed experiment, X-ray imaging and enzyme-linked immunosorbent assay analysis of serum inflammatory cytokines interleukin-1beta (IL-β), IL-6, and tumor necrosis factor-α (TNF-α) and anti-inflammatory cytokines interleukin-10 and transforming growth factor-beta (TGF-β) were carried out. In addition, RT-PCR was used to measure nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and type II collagen mRNA levels and Western blot analysis was used to determine caspase-3 protein levels in all treated groups. Finally, hematoxylin/and eosin stains were used for histopathological investigation. Administration of BM-MSCs significantly downregulated knee joint swelling and MIA-induced (IL-1β, IL-6, and TNF-α) and upregulated IL-10 and TGF-β as well. Moreover, BM-MSC-treated osteoarthritic rats exhibited decreased expression of NF-κB, iNOS, and apoptotic mediator (caspase-3) and increased expression of type II collagen when compared to rats treated with MIA alone. The hematoxylin/eosin-stained sections revealed that BM-MSC administration ameliorated the knee joint alterations in MIA-injected rats. BM-MSCs could be an effective treatment for inflamed knee joints in the MIA-treated rat model of osteoarthritis, and the effect may be mediated via its anti-inflammatory and antioxidant potential.

Nardosinone suppresses monoiodoacetate-induced osteoarthritis in rats: The key role of the miR-218-5p/NUMB axis.

Nardosinone is a bioactive compound with a sesquiterpenoid structure isolated from Nardostachys jatamansi. The compound has shown treatment effects against skeletal disorders. In the current study, the effects of nardosinone on osteoarthritis (OA) were first assessed and the mechanism underlying the effects was explored by detecting changes in the miR-218-5p/NUMB axis. The miR, as a potential target mediating the effects of nardosinone on OA, was first determined with microarray and RT-qPCR detections. Then, OA symptoms were induced in rats using monoiodoacetate (MIA) and treated with nardosinone. The anti-OA effects of nardosinone were assessed via the detection of the histological structure and inflammation. The role of miR-218-5p was delineated by modulating its levels in OA-affected rats. Based on the results of microarray and RT-qPCR detections, miR-218-5p was selected as the therapeutic target for nardosinone. The induction of OA resulted in tissue destruction and the production of cytokines in rat joint tissues, which was associated with the up-regulation of miR-218-5p and the downregulation of NUMB. For OA-affected rats treated with nardosinone, the joint structure was improved and the inflammatory response was suppressed, along with the restored expression levels of miR-218-5p and NUMB. The re-induced level of miR-218-5p compromised the anti-OA effects of nardosinone, indicating that the inhibition of the miR played an indispensable role in the anti-OA function of nardosinone. Collectively, the findings of our study demonstrated that nardosinone exerts treatment effects against OA by modulating the miR-218-5p/NUMB axis. Future studies will provide more detailed information on the interaction between nardosinone and miR in the attenuation of OA.

The effect of REV-ERB agonist on nociceptive hypersensitivity in monoiodoacetate-induced osteoarthritis model

The effect of REV-ERB agonist on nociceptive hypersensitivity in monoiodoacetate-induced osteoarthritis model

Changes of Grip Strength, Articular Cartilage and Subchondral Bone in Monoiodoacetate-Induced Osteoarthritis in Rats

Osteoarthritis is a degenerative disease affecting articular cartilage among the elderly. The intra-articular monoiodoacetate injection is one of the most widely used methods to induce osteoarthritis in animals. While the effects of monoiodoacetate on cartilage are well-characterized, its effects on subchondral bone remodeling are less studied. The purpose of this study was to determine the changes of the grip strength, articular cartilage structure and subchondral bone remodeling in monoiodoacetate-induced osteoarthritis in rats. Three-month-old male Wistar rats were assigned to normal control (n=6) and osteoarthritis group (n=6), which received intra-articular injection of 4 mg/50 µL monoiodoacetate solution once at the left knee of hindlimb. The rats were monitored for four weeks. The grip strength test was performed before injection and every week after injection. After four weeks, the femurs with intact cartilage were harvested for histomorphological analysis. Grip strength was reduced significantly in the osteoarthritic rats compared to the normal rats (p<0.05). Food intake was reduced significantly one week following monoiodoacetate-induction (p<0.05), but it stabilized afterwards. Monoiodoacetate injection increased cartilage erosion and osteoclast number in the subchondral bone of the osteoarthritic rats compared to the normal rats (p<0.05). However, it did not affect body weight, subchondral bone osteoblast activity, mineralization and microstructure of osteoarthritic rats (p>0.05). As a conclusion, monoiodoacetate-induced osteoarthritis affects the cartilage and increases osteoclast formation in the subchondral bone of rats.

Luteolin prevents monoiodoacetate-induced osteoarthritis in post-menopausal rats via protection of the cartilage

Purpose: To investigate the effectiveness of luteolin treatment in postmenopausal model of osteoarthritis (OA)Methods: Sprague-Dawley rats were divided into five groups. Luteolin was given orally to rats at doses of 50 and 100 mg/kg for 4 months, while aceclofenac was administered at a dose of 10 mg/kg. The antiinflammatory and anti-arthritic effects of luteolin and aceclofenac were determined using paw-withdrawal method. Knee joint thickness was measured using X-ray imaging. Pathological changes in bone slices were determined with immuno-histochemical evaluation. The levels of inflammatory cytokines were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis.Results: Oral ingestion of luteolin significantly reduced manifestations of OA and suppressed levels of serum cytokines (p < 0.05). Moreover, luteolin increased expression of bone marker protein and reduced the gene expression levels of matrix metalloproteinases (MMPs, p < 0.05), suggesting its protective effects on chondrocytes. Luteolin significantly reduced the production of inflammatory chemokines and cytokines (IFN-γ, IL-1, and IL-6). Histopathological examination showed that luteolindecreased pathological lesions in monoiodoacetate-mediated OA in ovariectomized rats, indicatingprevention of cartilage loss.Conclusion: These results suggest that luteolin exerts protective effects against monoiodoacetateinduced (MIA) OA in ovariectomized rats by suppressing the expressions of inflammation-related mediators (IL-1β, Cox-2, and PGE-2). Thus, luteolin is a prospective option for the suppression of postmenopausal OA in humans.

Suppression of joint pain in transient receptor potential vanilloid 4 knockout rats with monoiodoacetate-induced osteoarthritis.

Transient receptor potential vanilloid 4 (TRPV4) modulates osteoarthritic (OA) pain in animal models. However, the pathophysiological function of TRPV4 in regulating OA pain remains poorly understood. We developed TRPV4-knockout (TRPV4-KO) rats and assessed the effects of Trpv4 gene deficiency in a monoiodoacetate (MIA)-induced OA pain model (MIA rats) by examining pain-related behavior, pathological changes, and electrophysiological changes in dorsal root ganglion (DRG) neurons. The changes detected in TRPV4-KO rats were confirmed in wild-type rats using a TRPV4 antagonist. Transient receptor potential vanilloid 4-KO rats showed the same pain threshold as wild-type rats for thermal or pressure stimuli under normal conditions. Trpv4 gene deletion did not suppress the development of osteoarthritis pathologically in MIA rats. However, the OA-related mechanical pain behaviors observed in MIA rats, including decreased grip strength, increased mechanical allodynia, and reduced weight-bearing on the ipsilateral side, were completely suppressed in TRPV4-KO rats. The DRG neurons in wild-type but not TRPV4-KO MIA rats were depolarized with increased action potentials. Transient receptor potential vanilloid 4 antagonist treatments recapitulated the effects of genetic Trpv4 deletion. Transient receptor potential vanilloid 4 was sensitized in the DRG neurons of MIA rats and played a critical role in the development of OA pain. These results suggest that the inhibition of TRPV4 might be a novel potent analgesic strategy for treating OA pain.

Niacinamide and undenatured type II collagen modulates the inflammatory response in rats with monoiodoacetate-induced osteoarthritis

The current work aimed to examine the properties of oral supplementation of niacinamide and undenatured type II collagen (UCII) on the inflammation and joint pain behavior of rats with osteoarthritis (OA). Forty-nine Wistar rats were allocated into seven groups; control (no MIA), MIA as a non-supplemental group with monosodium iodoacetate (MIA)-induced knee osteoarthritis, MIA + undenatured type II collagen (UCII) at 4 mg/kg BW, MIA + Niacinamide at 40 mg/kg BW (NA40), MIA + Niacinamide at 200 mg/kg BW (NA200), MIA + UCII + NA40 and MIA + UCII + NA200. Serum IL‐1β, IL‐6, TNF-α, COMP, and CRP increased in rats with OA and decreased in UCII and NA groups (p < 0.05). Rats with osteoarthritis had greater serum MDA and knee joint MMP-3, NF-κB, and TGβ protein levels and decreased in treated groups with UCII and NA (p < 0.05). The rats with OA also bore elevated joint diameters with joint pain behavior measured as decreased the stride lengths, the paw areas, and the paw widths, and increased the Kellgren-Lawrence and the Mankin scores (p < 0.05) and decreased in UCII treated groups. These results suggest the combinations with the UCII + NA supplementation as being most effective and reduce the inflammation responses for most OA symptoms in rats.

Calcified cartilage revealed in whole joint by X-ray phase contrast imaging

ObjectiveX-ray Phase Contrast Imaging (PCI) is an emerging modality that will be in the next few years available in a wider range of preclinical set-ups. In this study, we compare this imaging technique with conventional preclinical modalities in an osteoarthritis mouse model. MethodPhase contrast technique was performed on 6 post-mortem, monoiodoacetate-induced osteoarthritis knees and 6 control knees. The mice knees were then imaged using magnetic resonance imaging and conventional micro computed tomography. Examples of imaging surrogate markers are reported: local distances within the articular space, cartilage surface roughness, calcified cartilage thickness, number, volume and locations of osteophytes. ResultsThanks to PCI, we can show in 3D calcified cartilage without contrast agent by a non-invasive technique. The phase contrast images reveal more details than conventional imaging techniques, especially at smaller scales, with for instance a higher number of micro-calcifications detected (57, 314 and 329 for MRI, conventional micro-CT and phase contrast imaging respectively). Calcified cartilage thickness was measured with a significant difference (p ​< ​0.01) between the control (23.4 ​± ​17.2 ​μm) and the osteoarthritis induced animal (46.9 ​± ​19.0 ​μm). ConclusionsX-ray phase contrast imaging outperforms the conventional imaging modalities for assessing the different tissue types (soft and hard). This new imaging modality seems to bring new relevant surrogate markers for following-up small animal models even for low-grade osteoarthritis.

The Gut Microbiota of Rats under Experimental Osteoarthritis and Administration of Chondroitin Sulfate and Probiotic

Osteoarthritis is a most widespread chronic degenerative joint disease that causes pain, cartilage deformation, and joint inflammation. Adverse alterations of intestinal microbiota like dysbiosis may lead to metabolic syndrome and inflammation, two important components of osteoarthritis progression. Aim. In this study we investigated the effect of chondroitin sulfate and probiotics on the gut microbiome in monoiodoacetate-induced osteoarthritis model in rats. Methods. The species and quantitative composition of feces were determined using diagnostic media with selective properties. Further identification of isolated microorganisms was carried out according to morphological, tinctorial, physiological and metabolic parameters. The results are presented in the form of lg CFU/g. Results. Induction of osteoarthritis caused significant increasing the number of opportunistic enterobacteria and lactose-negative Escherichia coli against the decreasing of lacto- and bifidobacteria that may indicate a dysbiotic condition. Coadministration of chondroitin sulfate and probiotic bacteria has led to improvement the quantitative composition of the gut microbiota in experimental animals, the numerous of Bifidobacterium, Lactobacillus were increasing against decreasing the quantitative composition of opportunistic microorganisms. Conclusions. Monoiodoacetate-induced osteoarthritis caused dysbiosis of gut in rat. We observed beneficial effect of combined administration of chondroitin sulfate and probiotics on gut microbiota composition in rats with experimental osteoarthritis. Thus, adding of supplements like probiotics to standard treatment of osteoarthritis may have potentials to prevent and treat this disease.

Targeted elimination of intracellular reactive oxygen species using nanoparticle-like chitosan- superoxide dismutase conjugate for treatment of monoiodoacetate-induced osteoarthritis.

In our previous work, cationic functionalized chitosan was chemically conjugated with superoxide dismutase (SOD) to yield a unique nanoparticle-like conjugate O-HTCC-SOD that has demonstrated superior potential in treating reactive oxygen species (ROS)-related disorders to SOD. Considering contribution of ROS to pathogenesis of osteoarthritis, O-HTCC-SOD was firstly measured for effect on rat chondrocytes exposure to monoiodoacetate (MIA). O-HTCC-SOD was nontoxic to chondrocytes and had more long-acting and intracellular protection effects on chondrocytes against MIA-induced oxidative damage due to its superior elimination of intracellular ROS to SOD. Pharmacokinetic analysis demonstrated that O-HTCC-conjugated SOD significantly prolonged half-life and residence in rat joint cavity, and improved bioavailability compared with unmodified SOD. Intra-articular injection of O-HTCC-SOD significantly attenuated mechanical allodynia in MIA-induced osteoarthritis rats, dramatically suppressed gross morphological and histological lesions of articular cartilage, and greatly enhanced in vivo antioxidant capacity and anti-inflammatory effect. But native SOD had no obvious therapeutic effects. Consequently, the nanoparticle-like conjugate O-HTCC-SOD of the excellent efficacy resulted from its targeted intracellular ROS clearance capability and improved pharmacokinetic profiles, opening up a novel avenue for disease-modifying osteoarthritis drugs.

MSC encapsulation in alginate microcapsules prolongs survival after intra-articular injection, a longitudinal in vivo cell and bead integrity tracking study

Mesenchymal stem cells (MSC) are promising candidates for use as a biological therapeutic. Since locally injected MSC disappear within a few weeks, we hypothesize that efficacy of MSC can be enhanced by prolonging their presence. Previously, encapsulation in alginate was suggested as a suitable approach for this purpose. We found no differences between the two alginate types, alginate high in mannuronic acid (High M) and alginate high in guluronic acid (High G), regarding MSC viability, MSC immunomodulatory capability, or retention of capsule integrity after subcutaneous implantation in immune competent rats. High G proved to be more suitable for production of injectable beads. Firefly luciferase-expressing rat MSC were used to track MSC viability. Encapsulation in high G alginate prolonged the presence of metabolically active allogenic MSC in immune competent rats with monoiodoacetate-induced osteoarthritis for at least 8 weeks. Encapsulation of human MSC for local treatment by intra-articular injection did not significantly influence the effect on pain, synovial inflammation, or cartilage damage in this disease model. MSC encapsulation in alginate allows for an injectable approach which prolongs the presence of viable cells subcutaneously or in an osteoarthritic joint. Further fine tuning of alginate formulation and effective dosage for might be required in order to improve therapeutic efficacy depending on the target disease.Graphical

Intraarticular injection of processed lipoaspirate cell has anti-inflammatory and analgesic effects in murine monoiodoacetate-induced osteoarthritis

Purpose: Osteoarthritis (OA) of the knee is common and one of the major causes of joint dysfunction and physical disability in the elderly. OA of the knee is associated with knee-related disabling symptoms in about 10% of UK men and women aged more than 55 years, and about 25% of these patients suffer debilitating disability. It was reported that 49.5% of elderly Japanese had radiographically-evident bilateral OA of the knee (Kellgren and Lawrence (K/L) grade ≥2). Furthermore, the estimated the prevalence of knee OA in Japan is 42.6% and 62.4%.

Cytokines profile in knee cartilage of rats during monoiodoacetate-induced osteoarthritis and administration of probiotic

Cytokines profile in knee cartilage of rats during monoiodoacetate-induced osteoarthritis and administration of probiotic

Ginsenoside Rb1 inhibits monoiodoacetate-induced osteoarthritis in postmenopausal rats through prevention of cartilage degradation

BackgroundGinsenoside Rb1 (G-Rb1), one of the major active compounds in Panax ginseng, has already been shown to reduce inflammation in various diseases. Osteoarthritis (OA) has traditionally been considered a degenerative disease with degradation of joint articular cartilage. However, recent studies have shown the association of inflammation with OA. In the present study, we investigated whether Rb1 had an antiinflammatory effect on monoiodoacetate (MIA)-induced OA in ovariectomized rats as a model of postmenopausal arthritis. MethodsG-Rb1 at a dosage of 3 and 10 μg/kg body weight was administered every 3 days intraarticularly for a period of 4 weeks to observe antiarthritic effects. Diclofenac (10 mg/kg) served as a positive control. ResultsThe administration of Rb1 significantly ameliorated OA inflammatory symptoms and reduced serum levels of inflammatory cytokines. Furthermore, G-Rb1 administration considerably enhanced the expression of bone morphogenetic protein-2 and collagen 2A and reduced the levels of matrix metalloproteinase-13 genes, indicating a chondroprotective effect of G-Rb1. G-Rb1 also significantly reduced the expression of several inflammatory cytokines/chemokines (interferon gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1)/CCL-2, interleukin [IL]-1β, and IL-6). Histological analysis demonstrated that G-Rb1 significantly attenuated the pathological changes in MIA-induced OA in ovariectomized rats. Safranin O and toluidine blue staining further demonstrated that G-Rb1 effectively prevented the degradation of cartilage and glycosaminoglycans, respectively. ConclusionOverall, our results suggest that G-Rb1 exerts cartilage protective effect on MIA-induced ovariectomized OA rats, by inhibiting inflammatory mediators such as IL-6, IL-1β, MCP-1/CCL-2, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). These results shed a light on possible therapeutic application of G-Rb1 in OA.