Rebamipide attenuates pain severity and cartilage degeneration in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes

Moon, Su‐Jin; Woo, Yun-Ju; Jeong, Jin‐Woo; Park, M.-K.; Oh, Hyeyoung; Park, J.-S.; Kim, E.-K.; Cho, M.-L.; Park, S.-H.; Kim, H.-Y.; Min, Jun‐Ki

doi:10.1016/j.joca.2012.08.002

Cited by 65 publications

(39 citation statements)

References 47 publications

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“…Cellular abnormalities were scored on a scale of 0–3: 0 normal; 1 hypercellularity, including small superficial clusters; 2 clusters; 3 hypocellularity. Matrix staining was scored on a scale of 0–4: 0 normal/slight reduction in staining; 1 reduced staining in the radial layer; 2 reduced staining in the interterritorial matrix; 3 staining present only in the pericellular matrix; 4 no staining [15]. Three independent observers assessed cartilage damage in a blinded manner.…”

Section: Methodsmentioning

confidence: 99%

Chondroprotective Effects of Ginsenoside Rg1 in Human Osteoarthritis Chondrocytes and a Rat Model of Anterior Cruciate Ligament Transection

et al. 2017

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This study aimed to assess whether Ginsenoside Rg1 (Rg1) inhibits inflammatory responses in human chondrocytes and reduces articular cartilage damage in a rat model of osteoarthritis (OA). Gene expression and protein levels of type II collagen, aggrecan, matrix metalloproteinase (MMP)-13 and cyclooxygenase-2 (COX-2) were determined in vitro by quantitative real-time-polymerase chain reaction and Western blotting. Prostaglandin E2 (PGE2) amounts in the culture medium were determined by enzyme-linked immunosorbent assay (ELISA). For in vivo assessment, a rat model of OA was generated by anterior cruciate ligament transection (ACLT). Four weeks after ACLT, Rg1 (30 or 60 mg/kg) or saline was administered by gavage once a day for eight consecutive weeks. Joint damage was analyzed by histology and immunohistochemistry. Ginsenoside Rg1 inhibited Interleukin (IL)-1β-induced chondrocyte gene and protein expressions of MMP-13, COX-2 and PGE2, and prevented type II collagen and aggrecan degradation, in a dose-dependent manner. Administration of Ginsenoside Rg1 to OA rats attenuated cartilage degeneration, and reduced type II collagen loss and MMP-13 levels. These findings demonstrated that Ginsenoside Rg1 can inhibit inflammatory responses in human chondrocytes in vitro and reduce articular cartilage damage in vivo, confirming the potential therapeutic value of Ginsenoside Rg1 in OA.

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Section: Methodsmentioning

confidence: 99%

Chondroprotective Effects of Ginsenoside Rg1 in Human Osteoarthritis Chondrocytes and a Rat Model of Anterior Cruciate Ligament Transection

et al. 2017

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“…These studies indicate that sphingosine kinase-2, Rho kinase, kinin B(2) receptors, and nAChR are involved in OA pain. Rebamipide, a free radical scavenger 62 , significantly inhibited MIA-induced pain and cartilage degeneration by decreasing MMP-13, IL-1β, hypoxia-inducible factor-2alpha (HIF-2α), inducible NO synthase (iNOS), and nitrotyrosine expression in OA cartilage and by increasing tissue inhibitor expression of MMP-1 and MMP-3 63 . This suggests that reactive oxygen species (ROS) are involved in OA pain.…”

Section: Peripheral Mechanismsmentioning

confidence: 99%

Osteoarthritis pain mechanisms: basic studies in animal models

Zhang

Ren

Dubner

2013

Osteoarthritis and Cartilage

137

112

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Osteoarthritis (OA) is a complex and painful disease of the whole joint. At present there are no satisfying agents for treating OA. The current standard of care mainly involves managing and alleviating its symptoms. Mechanisms of OA pain have been studied in rodent knee OA models produced by intra-knee injection of the chondrocyte glycolytic inhibitor mono-iodoacetate, surgery, or spontaneous development in some species. These models are clinically relevant in terms of histological damage and functional changes, and are used to study mechanisms underlying mechanical, thermal, ambulatory, body weight supporting-evoked, and ongoing OA pain. Recent peripheral, spinal, and supraspinal biochemical and electrophysiological studies in these models suggest that peripheral pro-inflammatory mediators and neuropeptides sensitize knee nociceptors. Spinal cytokines and neuropeptides promote OA-associated pain, and peripheral and spinal cannabinoids inhibit OA pain respectively through cannabinoid-1 (CB1) and CB1/CB2 receptors. TRPV1 and metalloproteinases contribute and supraspinal descending facilitation of 5-HT/5-HT 3 receptors may also contribute to OA pain. Conditioned place preference tests demonstrate that OA pain induces aversive behaviors suggesting brain involvement in OA pain. During OA, brain functional connectivity is enhanced, but at present it is unclear how this change is related to OA pain.

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“…24 Given its anti-apoptotic effect on neurons, LIG can be developed as an effective drug for the prevention of vascular dementia. 33 A decrease in iNOS is related to the amelioration of cartilage breakdown and chondrocyte apoptosis, which has been verified to relieve pain and inflammation related to OA symptoms. LIG inhibited chondrocyte apoptosis and ameliorated cartilage degeneration via the JNK and p38 mitogen-activated protein kinas (MAPK) signalling pathways, leading to the down-regulation of inducible nitric oxide synthase (iNOS) and p-activating transcription factor 2 (ATF2) expression mitochondrial function deletion may be prior to the process of apoptosis.…”

Section: Discussionmentioning

confidence: 97%

Ligustilide attenuates nitric oxide‐induced apoptosis in rat chondrocytes and cartilage degradation via inhibiting JNK and p38 MAPK pathways

Zhou

Jiang

et al. 2019

J Cellular Molecular Medi

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Ligustilide ( LIG ) is the main lipophilic component of the Umbelliferae family of pharmaceutical plants, including Radix angelicae sinensis and Ligusticum chuanxiong. LIG shows various pharmacological properties associated with anti‐inflammation and anti‐apoptosis in several kinds of cell lines. However, the therapeutic effects of LIG on chondrocyte apoptosis remain unknown. In this study, we investigated whether LIG had an anti‐apoptotic activity in sodium nitroprusside ( SNP )‐stimulated chondrocyte apoptosis and could delay cartilage degeneration in a surgically induced rat OA model, and elucidated the potential mechanisms. In vitro studies revealed that LIG significantly suppressed chondrocyte apoptosis and cytoskeletal remodelling, which maintained the nuclear morphology and increased the mitochondrial membrane potential. In terms of SNP , LIG treatment considerably reduced the expression levels of cleaved caspase‐3, Bax and inducible nitric oxide synthase and increased the expression level of Bcl‐2 in a dose‐dependent manner. The LIG ‐treated groups presented a significantly suppressed expression of activating transcription factor 2 and phosphorylation of Jun N‐terminal kinase ( JNK ) and p38 mitogen‐activated protein kinase ( MAPK ). The inhibitory effect of LIG was enhanced by the p38 MAPK inhibitor SB 203580 or the JNK inhibitor SP 600125 and offset by the agonist anisomycin. In vivo studies demonstrated that LIG attenuated osteoarthritic cartilage destruction by inhibiting the cartilage chondrocyte apoptosis and suppressing the phosphorylation levels of activating transcription factor 2, JNK and p38 MAPK . This result was confirmed by histological analyses, micro‐ CT , TUNEL assay and immunohistochemical analyses. Collectively, our studies indicated that LIG protected chondrocytes against SNP ‐induced apoptosis and delayed articular cartilage degeneration by suppressing JNK and p38 MAPK pathways.

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Rebamipide attenuates pain severity and cartilage degeneration in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes

Cited by 65 publications

References 47 publications

Chondroprotective Effects of Ginsenoside Rg1 in Human Osteoarthritis Chondrocytes and a Rat Model of Anterior Cruciate Ligament Transection

Chondroprotective Effects of Ginsenoside Rg1 in Human Osteoarthritis Chondrocytes and a Rat Model of Anterior Cruciate Ligament Transection

Osteoarthritis pain mechanisms: basic studies in animal models

Ligustilide attenuates nitric oxide‐induced apoptosis in rat chondrocytes and cartilage degradation via inhibiting JNK and p38 MAPK pathways

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