scholarly journals Therapeutic Effect of Matrine on Collagen-Induced Arthritis Rats and Its Regulatory Effect on RANKL and OPG Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xin Li ◽  
Lijie Zhang ◽  
Yongsong Xu ◽  
Dong Zhao ◽  
Lin Mu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Joint Damage ◽  
Bone Destruction ◽  
Blood Analysis ◽  
Drug Candidate ◽  
Control Group ◽  
Regulatory Effect ◽  
Rankl Expression ◽  
Collagen Induced Arthritis ◽  
X Ray

Objective. To investigate the effect of matrine on rats with collagen-induced arthritis (CIA) and its regulatory effect on receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) expression. Methods. Wistar rats ( n = 6 ) and CIA rats ( n = 30 ) were randomly divided into six groups: healthy, CIA control, low/medium/high matrine (25, 50, or 100 mg/kg, once per day for six weeks), and methotrexate (MTX) (2 mg/kg, once per week for six weeks). The degree of joint damage was evaluated by X-ray and HE staining. Bone marrow suppression was assessed by routine blood analysis. In addition, the levels of serum RANKL and OPG in the rats were measured by ELISA. Results. The level of joint swelling and degree of joint damage assessed by ankle swelling measurements, AI score, X-ray, and HE staining were alleviated in the CIA rats treated with MTX or different doses of matrine. Furthermore, no obvious inhibitory effect was observed on the bone marrow of the CIA rats, regardless of the dose of matrine or treatment with 2 mg/kg MTX ( P > 0.05 ). The levels of OPG in serum and the ratio of OPG/RANKL were higher, and RANKL expression was lower in the low/medium/high matrine group compared with that of the CIA control group. The serum levels of OPG and OPG/RANKL ratio increased with the matrine dose, while the opposite was observed for RANKL expression. Conclusion. Matrine treatment was associated with a lower degree of bone destruction, increased OPG expression and OPG/RANKL ratio, and decreased RANKL expression in CIA rats. Thus, matrine may represent a novel drug candidate for the treatment of RA.

Total Flavonoids of Bidens pilosa Ameliorates Bone Destruction in Collagen-Induced Arthritis

Planta Medica ◽  
2021 ◽  
Author(s):  
Mengqin Hong ◽  
Xingyu Fan ◽  
Shengxiang Liang ◽  
Wang Xiang ◽  
Liting Chen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Proinflammatory Cytokines ◽  
Bone Destruction ◽  
Nuclear Factor Κb ◽  
Total Flavonoids ◽  
Nuclear Factor ◽  
Collagen Induced Arthritis ◽  
Bidens Pilosa ◽  
X Ray ◽  
Receptor Activator

AbstractRheumatoid arthritis is a chronic autoimmune disease characterized by the infiltration of synovial inflammatory cells and progressive joint destruction. Total flavonoids of Bidens pilosa have been used against inflammation in rheumatoid arthritis, but its role in bone destruction remains to be explored. The aim of this paper was to study whether total flavonoids of B. pilosa relieve the severity of collagen-induced arthritis in rats, particularly whether it regulates the production of proinflammatory cytokines and the receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin signaling pathway. In this research, a collagen-induced disease model was induced in adult rats by subcutaneous injection of collagen II. Total flavonoids of B. pilosa at different doses (40, 80, and 160 mg/kg/d) were administered intragastrically, while methotrexate (1 mg/kg/w) was injected intraperitoneally as a positive control. Paw swelling, arthritis score, and body weight were assessed and evaluated. The severity of joint damage was determined using X-ray and confirmed by histopathology. The expression levels of receptor activator of nuclear factor-κB ligand, osteoprotegerin, IL-1β, IL-17, and TNF in the serum and tissue were assayed using ELISA and immunohistochemistry. We found that total flavonoids of B. pilosa attenuated collagen-induced arthritis at the macroscopic level, and total flavonoids of B. pilosa-treated rats showed reduced paw swelling, arthritis scores, and X-ray appearance of collagen-induced arthritis in addition to improved histopathological results. These findings were consistent with reduced serum and tissue receptor activator of nuclear factor-κB ligand, TNF, IL-1β, and IL-17 levels but increased osteoprotegerin levels. Our data suggest that total flavonoids of B. pilosa attenuate collagen-induced arthritis by suppressing the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin pathway and the subsequent production of proinflammatory cytokines. In addition, total flavonoids of B. pilosa may be a promising therapeutic candidate for the management of rheumatoid arthritis.

scholarly journals The Results of Fetal Chondrocytes Transplantation in Patients with Rheumatoid Arthritis

2014 ◽  
Vol 3 ◽  
Author(s):  
Natalya Krivoruchko ◽  
Saltanat Tuganbekova ◽  
Gulnar Rakhimbekova ◽  
Karlygash Kuzembaeva ◽  
Lina Zaripova
Keyword(s):  
Rheumatoid Arthritis ◽  
Morphological Changes ◽  
Control Cell ◽  
Clinical Manifestations ◽  
Bone Destruction ◽  
Human Embryos ◽  
Control Group ◽  
X Ray ◽  
Donor Cells

Introduction. Nowadays anti-inflammatory and immunosuppressive therapy has significantly improved the quality of life and prognosis of rheumatoid arthritis (RA). Nevertheless, there are still many patients with progressive rheumatoid inflammation, resulting in the destruction of joints. Cell therapy seems like a promising direction in rheumatology. The aim of our research was to evaluate the efficacy of fetal chondrocyte transplantation in patients with RA.Methods. We examined 60 patients with rheumatoid arthritis (I - III stages) between 20 and 63 years of age. They were divided into 2 groups: the first group underwent the fetal chondrocytes transplantation (n = 40), and the second was a control group who got conservative therapy (n = 20). Donor cells were taken from the chondrogenic layer of the humerus or femur heads and hip condyles of human embryos in gestation for 17-20 weeks. A suspension of fetal chondrocytes injected into affected areas of the articular surfaces under X-ray control. Cell viability was determined before the injection. Efficacy of the therapy was assessed by clinical, instrumental, and laboratory tests. This clinical trial was allowed by The Ministry of Public Health and Ethics Committee. All of our patients gave informed consent for the fetal chondrocytes transplantation.Results. Evaluation of the clinical manifestations of RA in the first group of patients showed 3.7 times decrease in pain and 1.6 times relief of synovitis. Complete reduction of contracture was observed in 82% of patients in the first group. Morphometric changes in X-ray demonstrated inhibition of the destruction in articular cartilage and surfaces of bones after transplantation of fetal chondrocytes. The dynamics of morphological changes in synovium showed 2.5 times reduction of the inflammatory reaction. Transplantation of fetal chondrocytes led to a significant reduction in ESR, CRP, fibrinogen , γ-globulin after a period of 12 months (p < 0.03). Furthermore, patients in the second group had 2.7 times higher risk of ankylosis compared to the first group. We did not observe any complications of fetal chondrocytes transplantation.Conclusions. Application of fetal chondrocytes therapy had the desired clinical effect, which was confirmed by reduction of the RA activity and decrease of cartilage and bone destruction. 

scholarly journals Propionibacterium freudenreichii Inhibits RANKL-Induced Osteoclast Differentiation and Ameliorates Rheumatoid Arthritis in Collagen-Induced Arthritis Mice

2021 ◽  
Vol 10 (1) ◽  
pp. 48
Author(s):  
Jiah Yeom ◽  
Dong Joon Yim ◽  
Seongho Ma ◽  
Young-Hee Lim
Keyword(s):  
Rheumatoid Arthritis ◽  
Mouse Model ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Joint Damage ◽  
Bone Destruction ◽  
In Vivo Studies ◽  
Propionibacterium Freudenreichii ◽  
Limited Information ◽  
Collagen Induced Arthritis

Osteoclast differentiation is crucial for bone absorption, and osteoclasts are involved in bone destruction in rheumatoid arthritis (RA). Dairy Propionibacterium freudenreichii is used as a cheese starter and possesses prebiotic and postbiotic properties. It is known to stimulate the growth of bifidobacteria and produces valuable metabolites, such as vitamin B12 and propionic acid. However, limited information is available on the beneficial effects of P. freudenreichii on human disease. Herein, we aimed to investigate the inhibitory effect of P. freudenreichii MJ2 (MJ2) isolated from raw milk on osteoclast differentiation and evaluate the improvement in RA. The murine macrophage cell line, RAW 264.7, and a collagen-induced arthritis (CIA) mouse model were used to perform in vitro and in vivo studies, respectively. Heat-killed P. freudenreichii MJ2 (hkMJ2)-treated cells significantly inhibited RANKL-induced osteoclast differentiation and TRAP activity. HkMJ2-treated cells exhibited significantly decreased expression of genes and proteins related to RANKL-induced osteoclast differentiation. MJ2 administration decreased the arthritic score in the CIA mouse model. Live and dead MJ2 inhibited bone loss and afforded protection against bone erosion and joint damage in CIA mice. MJ2 decreased the levels of collagen-specific antibodies and inflammatory cytokines and the expression of osteoclast differentiation-related genes and proteins in CIA mice. Interestingly, live and dead MJ2 showed similar RA improvement effects in CIA mice. In conclusion, P. freudenreichii MJ2 inhibited osteoclast differentiation by inhibiting the NF-κB signaling pathway and ameliorated CIA.

scholarly journals IL-38 restrains inflammatory response of collagen-induced arthritis in rats via SIRT1/HIF-1α signaling pathway

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Bing Pei ◽  
Keyan Chen ◽  
Shenglai Zhou ◽  
Dongyu Min ◽  
Weiguo Xiao
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Joint Damage ◽  
Inhibitory Effect ◽  
Angiogenic Factor ◽  
Inflammatory Factors ◽  
Control Group ◽  
Collagen Induced Arthritis ◽  
Related Proteins

Abstract Objective: To observe the restraining effect of IL-38 on inflammatory response in collagen-induced arthritis rats (CIA), and to explore the regulatory mechanism of SIRT1/HIF-1α signaling pathway. Methods: 40 SD rats were randomly divided into Control group, CIA group, CLL group and CLH group, with 10 rats in each group; CIA rat model was established. The effects of IL-38 on arthritis index, inflammatory response, osteogenic factor and angiogenic factor were observed by methods including HE staining, ELISA, immunohistochemical and immunofluorescence. Human synoviocytes were cultured in vitro, and SIRT1 inhibitors were added to detect the expression for relating factors of SIRT1/HIF-1α signaling pathway by Western blot. Results: IL-38 could alleviate CIA joint damage and restrain inflammatory response, could up-regulate the expression of OPG in CIA rats and could down-regulate the expression of RANKL and RANK. IL-38 could restrain the expression of VEGF, VEGFR1, VEGFR2 and HIF. Moreover, we found that IL-38 could up-regulate the SIRT1 expression and down-regulate the HIF-1α, TLR4 and NF-KB p65 expression in CLL and CLH groups. From the treatment of synoviocytes to simulate the CIA model and the treatment of SIRT1 inhibitors, we demonstrated that the inhibitory effect of IL-38 on inflammatory factors and regulation of SIRT1/HIF-1α signaling pathway-related proteins were inhibited. Conclusion: IL-38 can restrain the inflammatory response of CIA rats, can promote the expression of osteogenic factors, can inhibit neovascularization, and can alleviate joint damage in rats. The mechanism may be related to the regulation of SIRT1/HIF-1α signaling pathway.

scholarly journals Shexiang-Wulong Pills Attenuate Rheumatoid Arthritis by Alleviating Inflammation in a Mouse Model of Collagen-Induced Arthritis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zhihui Zhang ◽  
Ying Cao ◽  
Qiang Yuan ◽  
Aiguo Zhang ◽  
Kaiqi Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Song Dynasty ◽  
Bone Destruction ◽  
Serum Levels ◽  
Treated Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Group Model ◽  
Model Group ◽  
Collagen Induced Arthritis

Shexiang-Wulong Pill (SWP) is derived from “Moschus Yuan,” first formulated during the Song Dynasty for the treatment of joint pain. The aim of this study was to evaluate the therapeutic effect of SWP in a mouse model of collagen-induced arthritis (CIA). Forty-five DBA/1 mice were randomly divided into control group, model group, and SWP-treated group. SWP was administered by oral gavage for 22 days after the booster immunization. The clinical arthritic scores and joint histopathology, including synovial hyperplasia and hypoxic regions, cartilage erosion, and bone destruction, were evaluated. Microcomputed tomography (micro-CT) was used to assess microstructural changes in the bone. Serum levels of TNF-a, IL-6, and IFN-γ were measured by enzyme-linked immunosorbent assay (ELISA). The results showed a statistically significant improvement in joint pathological changes in the SWP-treated group. Imaging assessment confirmed that SWP protected the bone tissue from CIA-induced erosion and increased the bone density. In addition, the serum levels of TNF-a, IL-6, and IFN-γ in SWP-treated mice were significantly lower than those in the model group (P<0.05). Taken together, Shexiang-Wulong Pill can effectively alleviate joint swelling in CIA mice, inhibit synovial tissue hyperplasia, reduce inflammatory cell infiltration, and delay bone destruction. These results indicate that Shexiang-Wulong Pills could be an efficient medication for the treatment of RA.

scholarly journals Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotrexate on Collagen-Induced Arthritis in Cynomolgus Monkeys

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Hiroyuki Yamada ◽  
Hiroshi Mori ◽  
Yasutomo Nakanishi ◽  
Satoshi Nishikawa ◽  
Yasuaki Hashimoto ◽  
...  
Keyword(s):  
Joint Destruction ◽  
Cathepsin K ◽  
Type Ii Collagen ◽  
Control Group ◽  
Type I ◽  
Type Ii ◽  
Collagen Induced Arthritis ◽  
Cynomolgus Monkeys ◽  
X Ray ◽  
Cathepsin K Inhibitor

We examined whether the cathepsin K inhibitor, ONO-5334, administered alone or in combination with methotrexate (MTX), could ameliorate joint destruction evoked by collagen-induced arthritis (CIA) in female cynomolgus monkeys. CIA was induced by immunizing with bovine type II collagen. ONO-5334 (30 mg/kg/day) was orally administered once daily and MTX (10 mg/body/day) twice weekly for 9 weeks. X-ray (evaluation of joint destruction) and swelling (inflammatory) scores of proximal interphalangeal (PIP), distal interphalangeal (DIP), and metacarpophalangeal (MP) joints were evaluated. Urinary concentrations of C-terminal telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) were measured. Arthritis, accompanied by bone and cartilage destruction, was successfully induced in this collagen-induced arthritis monkey model. ONO-5334 showed no suppressive effect on joint swelling, while the joint swelling scores in the MTX and combination (ONO-5334 + MTX) groups were less than 50% compared with the control group. ONO-5334 decreased X-ray score by a mean of 64% (p<0.05 vs the control group), and MTX also decreased in X-ray score by a mean of 46% but with no statistical significance. Combination of ONO-5334 and MTX further decreased the X-ray score by 28% over MTX group (74% reduction vs the control group, p<0.01). Maximum increase in CTX-I (10-fold) and CTX-II (7-fold) compared to baseline was observed at 7 and 3 weeks after the first sensitization, respectively. After treatment with ONO-5334 alone or in combination with MTX, concentrations were maintained near baseline for both markers. In conclusion, ONO-5334 prevented joint destruction but not joint inflammation in this monkey CIA model. Concomitant use of ONO-5334 with MTX reduced architectural joint destruction compared to MTX alone; therefore, ONO-5334 may help to prevent joint destruction in combination with MTX for the treatment of rheumatoid arthritis.

The natural flavonoid galangin inhibits osteoclastic bone destruction and osteoclastogenesis by suppressing NF-κB in collagen-induced arthritis and bone marrow-derived macrophages

2013 ◽  
Vol 698 (1-3) ◽  
pp. 57-66 ◽  
Author(s):  
Jeong-Eun Huh ◽  
In-Tae Jung ◽  
Junyoung Choi ◽  
Yong-Hyeon Baek ◽  
Jae-Dong Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Destruction ◽  
Collagen Induced Arthritis

scholarly journals Investigation of Protective Effects of Quercetin on Oxidative Stress Induced by Vinblastine in Bone Marrow of Rats

2020 ◽  
Vol 27 (2) ◽  
pp. 194-200
Author(s):  
Hamed Aramjoo ◽  
Habibollah Ebrahim Zadeh ◽  
Mina Hemmati
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Single Dose ◽  
Antioxidant Capacity ◽  
Total Antioxidant Capacity ◽  
Therapeutic Potential ◽  
Blood Analysis ◽  
Control Group ◽  
Chemotherapy Drugs ◽  
Total Antioxidant

Background: Chemotherapy drugs such as vinblastine cause oxidative stress in the bone marrow resulting changes in blood cell production and anemia. In this study, the antioxidant and therapeutic potential of quercetin was evaluated. Methods: Twenty-one male Wistar rats were divided into three groups; The Control group received a daily dose of normal saline, group 2 received a single dose of 2 mg/kg b.w. vinblastine intraperitoneally (i.p.) on the first day of study, and group 3 received a single dose of vinblastine (2mg/kg b.w. i.p.) along with quercetin (20 mg/kg b.w. i.p.) for 14 days. To evaluate oxidative stress in bone marrow; malondialdehyde (MDA), Total Antioxidant Capacity (TAC) and Pro-Oxidant/Antioxidant Balance (PAB) were also measured using specified methods. Results: The blood analysis showed that the mean level of RBC, Hemoglobin, and Hematocritwere significantly higher in the vinblastine group compared to the control group. Treatment with quercetin could elevate them into the normal range. Administration of vinblastine elevated the levels of bone marrow MDA and PAB significantly (p<0.05) compared to the control group but had no effect on total antioxidant capacity. The use of quercetin with vinblastine showed a decrease in the levels of bone marrow MDA and PAB compared to the vinblastine group alone. Conclusion: The findings of this study showed that quercetin at a dose of 20 mg/kg could improve the anemia induced by vinblastine chemotherapy, and it can also be useful in improving vinblastine-induced lipotoxicity.

scholarly journals Anti-inflammatory Activity of Formononetin in a Collagen-induced Arthritis Mouse Model ofRheumatoid Arthritis

2020 ◽  
Author(s):  
Ying Zhao ◽  
GUIWU QU ◽  
Wenxue Lu ◽  
Qing Lv ◽  
Wenxing Shi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Erosion ◽  
Bone Destruction ◽  
Treated Group ◽  
Control Group ◽  
High Dose ◽  
Collagen Induced Arthritis ◽  
Hind Limbs ◽  
Healthy Control ◽  
Anti Inflammatory

Abstract Background: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation of the joints, leading to bone erosion and joint dysfunction. Although there are options for the treatment of RA, safer and more effective drugs are still being sought. Formononetin (FMN) is an isoflavonoid compound found in various plants, such as Astragalus propinquus Schischkin and Spatholobus suberectus. It has anti-tumor, anti-bacterial, anti-lipid peroxidation, and estrogen-like activities，and is a noteworthy compound for screening of anti-RA drugs. Methods: To investigate the anti-inflammatory effects of FMN in a collagen-induced arthritis (CIA) mouse model, thirty-six C57BL/6 mice were randomly divided into 6 groups: a healthy control group and 5 CIA groups. Arthritis was induced the CIA groups using chicken collagen type II. The CIA groups were divided in a control group (RA), a tripterygium glycosides (10 mg/kg body weight) treated group (TG), a low-dose (50 mg/kg) FMN group (FMN-L), a middle-dose(100mg/kg) FMN group (FMN-M), and a high-dose (200 mg/kg) FMN group (FMN-H). The control mice and CIA mice in the RA group were treated with an equal volume of 5% carboxymethylcellulose sodium. Drugs were delivered three times a week for four weeks, and the bodyweight, food-uptake, and swelling of the paws were monitored during the treatment process. Inflammatory cytokines and other biochemical indexes in the serum and joint tissues were analyzed, along with the expression levels of NF-κB pathway-related proteins (IκBα, p65, p-p65, TIPE2, and PCNP) in the spleen. Histopathological examinations were processed for the hind limbs. Results: FMN-M dramatically reduced the arthritis index in the CIA mice, inhibited the inflammatory cell infiltration, and prevented damage to the synovium and cartilage. Mechanistic studies suggested that FMN might reduce inflammation by inhibiting IκB-α degradation and by regulating the expression and release of NF-κB p65. Conclusions: These data suggest that FMN might be an active therapeutic agent for RA by preventing bone destruction, regulating inflammatory mediators, and suppressing NF-κB signaling pathways.

scholarly journals Phase II Multicenter Randomized Controlled Clinical Trial on the Efficacy of Intra-articular Injection of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet Rich Plasma for the Treatment of Knee Osteoarthritis

2020 ◽  
Author(s):  
José María Lamo-Espinosa ◽  
Juan F. Blanco ◽  
Mikel Sánchez ◽  
Victoria Moreno ◽  
Froilán Granero-Moltó ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Clinical Trials ◽  
Knee Osteoarthritis ◽  
Stromal Cells ◽  
Platelet Rich Plasma ◽  
Joint Damage ◽  
X Ray ◽  
The Mean

Abstract Background Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100x10 6 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF ® ) as adjuvant in a randomized clinical trial. Methods A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF ® or intraarticular administration of 100x10 6 cultured autologous BM-MSCs plus PRGF ® . Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. Results No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF ® and BM-MSC with PRGF ® went from 5 (1.8) to 4.5 (2.2) (p=0.389) and from 5.3 (1.9) to 3.5 (2.5) (p=0.01), respectively at 12 months.. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF ® was 31.9 (16.2) and 22.3 (15.8) respectively (p=0.002) while that for patients treated with BM-MSC plus PRGF ® was 33.4 (18.7) and 23.0 (16.6) (p=0.053). Although between groups statistically significances have been not detected, only patients being treated with BM-MSC plus PRGF ® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage. Conclusions Treatment with BM-MSC associated with PRGF ® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy.

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