scholarly journals Expression of osteopontin at sites of bone erosion in a murine experimental arthritis model of collagen-induced arthritis: Possible involvement of osteopontin in bone destruction in arthritis

2002 ◽  
Vol 46 (4) ◽  
pp. 1094-1101 ◽  
Author(s):  
Shiro Ohshima ◽  
Hideyuki Kobayashi ◽  
Norihiko Yamaguchi ◽  
Katsuhiro Nishioka ◽  
Mitsuko Umeshita-Sasai ◽  
...  
2010 ◽  
Vol 31 (5) ◽  
pp. 595-603 ◽  
Author(s):  
Samjin Choi ◽  
Yeon-Ah Lee ◽  
Seung-Jae Hong ◽  
Gi-Ja Lee ◽  
Sung Wook Kang ◽  
...  

2020 ◽  
Vol 21 (9) ◽  
pp. 3230
Author(s):  
Hyun Jung Yoo ◽  
Won Chan Hwang ◽  
Do Sik Min

Phospholipase D1 (PLD1) plays a crucial role in various inflammatory and autoimmune diseases. Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease. However, the role of PLD1 in the pathogenesis of RA remains unknown. Here, we first investigated the role and effects of PLD1 in collagen-induced arthritis (CIA) and found that genetic and pharmacological inhibition of PLD1 in DBA1/J mice with CIA reduced the incidence of CIA, decreased the clinical score, and abrogated disease symptoms including infiltration of leukocytes, synovial inflammation, bone erosion, and cartilage destruction. Moreover, ablation and inhibition of PLD1 suppressed the production of type II collagen-specific IgG2a autoantibody and proinflammatory cytokines, accompanied by an increase in the regulatory T (Treg) cell population and a decrease in the Th17 cell population in CIA mice. The PLD1 inhibitor also promoted differentiation of Treg cells and suppressed differentiation of Th17 cells in vitro. Furthermore, the PLD1 inhibitor attenuated pathologic bone destruction in CIA mice by suppressing osteoclastogenesis and bone resorption. Thus, our findings indicate that the targeting of PLD1 can ameliorate CIA by modulating the imbalance of Treg and Th17 cells and suppressing osteoclastogenesis, which might be a novel strategy to treat autoimmune diseases, such as RA.


2021 ◽  
Vol 10 (1) ◽  
pp. 48
Author(s):  
Jiah Yeom ◽  
Dong Joon Yim ◽  
Seongho Ma ◽  
Young-Hee Lim

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.


2019 ◽  
Vol 6 (1) ◽  
pp. e000331 ◽  
Author(s):  
Ze-Min Lin ◽  
Yu-Ting Liu ◽  
Yan-Sheng Xu ◽  
Xiao-Qian Yang ◽  
Feng-Hua Zhu ◽  
...  

ObjectiveRheumatoid arthritis is an autoimmune disease characterised by inflammation and bone loss, leading to joint destruction and deformity. The cervus and cucumis polypeptide (CCP) injection, one of the traditional Chinese medicine injections combined extracts from deer horn and sweet melon seeds, is widely used to treat arthritis and bone fracture in China. The present study investigated the therapeutic efficacy and mechanism of CCP on pathological immune cells and bone homoeostasis in rodent experimental arthritis.MethodsThe effects of CCP (4 mg/kg and 2 mg/kg) on clinical arthritis symptoms, bone erosion, proinflammatory cytokines and pathological immune cells induced by complete Freund’s adjuvant was evaluated in male Sprague-Dawley rats. The impacts of CCP (2 mg/kg) on joint erythema and swelling, production of pathogenic antibodies and the proportion of inflammatory cells were assessed in collagen-induced arthritis (CIA) in DBA/1J mice. Regulation of osteoclastogenesis by CCP was observed in the murine macrophage-like RAW264.7 cells treated with receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF).ResultsCCP administration significantly prevented disease progression in both adjuvant-induced arthritis (AIA) rats and CIA mice. The therapeutic benefits were accompanied by reduction of paw oedema, reversed bone destruction, decreased pathological changes and osteoclast numbers in joints in AIA rats, as well as attenuated clinical manifestation and autoantibodies production in CIA mice. Meanwhile, in vitro supplemented of CCP concentration dependently inhibited RANKL/M-CSF-induced osteoclast differentiation, without showing cytotoxicity in RAW264.7 cells. Further, the presence of CCP dampened the augmented downstream signalling transduction as well as activation of osteoclast-specific genes and transcription factors induced by RANKL/M-CSF in RAW264.7 cells.ConclusionOur study suggested that the therapeutic effects of CCP in experimental arthritis could be attributed to its intervention on RANKL-induced osteoclastogenesis signalling pathway in osteoclast precursor cells.


2011 ◽  
Vol 38 (9) ◽  
pp. 1844-1857 ◽  
Author(s):  
YU-CHIEH HSU ◽  
CHIA-PI CHENG ◽  
DEH-MING CHANG

Objective.Plectranthus amboinicus has been known to treat inflammatory diseases or swelling symptoms. We investigated whether P. amboinicus exhibited an inhibitory effect on osteoclastogenesis in vitro and inflammatory bone erosion in collagen-induced arthritis (CIA) mice, an animal model of rheumatoid arthritis. We attempted to identify the active component of P. amboinicus involved in regulation of osteoclastogenesis.Methods.We treated M-CSF- and RANKL-stimulated murine bone marrow-derived macrophages (BMM) and RANKL-induced RAW264.7 cells with different concentrations of P. amboinicus or rosmarinic acid, a phytopolyphenol purified from P. amboinicus, to monitor osteoclast formation by TRAP staining. The mechanism of the inhibition was studied by biochemical analysis such as RT-PCR and immunoblotting. CIA mice were administered gavages of P. amboinicus (375 mg/kg) or placebo. Then clinical, histological, and biochemical measures were assessed to determine the effects of P. amboinicus on synovial inflammation and bone erosion by H&E staining of the inflamed joints and ELISA.Results.Rosmarinic acid strongly inhibited RANKL-induced NF-κB activation and nuclear factor of activated T cells c1 (NFATc1) nuclear translocation in BMM, and also inhibited RANKL-induced formation of TRAP-positive multinucleated cells. A pit formation assay and the CIA animal model showed that P. amboinicus significantly inhibited the bone-resorbing activity of mature osteoclasts.Conclusion.We postulated that rosmarinic acid conferred the inhibitory activity on P. amboinicus for inhibition of osteoclastogenesis via downregulation of RANKL-induced NFATc1 expression. Our results indicated the possibility of P. amboinicus as a new remedy against inflammatory bone destruction.


2020 ◽  
Author(s):  
Ying Zhao ◽  
GUIWU QU ◽  
Wenxue Lu ◽  
Qing Lv ◽  
Wenxing Shi ◽  
...  

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.


2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Rafael Scaf de Molon ◽  
Rogier M. Thurlings ◽  
Birgitte Walgreen ◽  
Monique M. Helsen ◽  
Peter M. van der Kraan ◽  
...  

Specialized proresolving mediators (SPRM), which arise from n-3 long-chain polyunsaturated fatty acids (n-3FA), promote resolution of inflammation and may help to prevent progression of an acute inflammatory response into chronic inflammation in patients with arthritis. Thus, this study is aimed at determining whether systemic RvE1 treatment reduces arthritis onset and severity in murine collagen-induced arthritis (CIA) and spontaneous cytokine production by human rheumatoid arthritis (RA) synovial explants. 10-week-old DBA1/J male mice were subjected to CIA and treated systemically with 0.1 μg RvE1, 1 μg RvE1, 5 mg/kg anti-TNF (positive control group), PBS (negative control group), or with a combination of 1 μg of RvE1 plus 5 mg/kg anti-TNF using prophylactic or therapeutic strategies. After CIA immunization, mice were treated twice a week by RvE1 or anti-TNF for 10 days. Arthritis development was assessed by visual scoring of paw swelling and histology of ankle joints. Moreover, human RA synovial explants were incubated with 1 nM, 10 nM, or 100 nM of RvE1, and cytokine levels (IL-1β, IL-6, IL-8, IL-10, INF-γ, and TNF-α) were measured using Luminex bead array. CIA triggered significant inflammation in the synovial cavity, proteoglycan loss, and cartilage and bone destruction in the ankle joints of mice. Prophylactic and therapeutic RvE1 regimens did not ameliorate CIA incidence and severity. Anti-TNF treatment significantly abrogated signs of joint inflammation, bone erosion, and proteoglycan depletion, but additional RvE1 treatment did not further reduce the anti-TNF-mediated suppression of the disease. Treatment with different concentrations of RvE1 did not decrease the expression of proinflammatory cytokines in human RA synovial explants in the studied conditions. Collectively, our findings demonstrated that RvE1 treatment was not an effective approach to treat CIA in DBA1/J mice in both prophylactic and therapeutic strategies. Furthermore, no effects were noticed when human synovial explants were incubated with different concentrations of RvE1.


Author(s):  
Francesco Ricotta ◽  
Massimo Bassi ◽  
Nicola Tomasetti ◽  
Angelo Campobassi ◽  
Vincenzo Maiolo ◽  
...  

: Osteosarcoma of the jaws (OSJ) is a relatively rare disease, accounting for between 2% and 10% of all cases of osteosarcoma, it is morphologically and radiologically identical to the trunk and extremity variant, but distinct in several crucial aspects. : The lesion is characterized by sarcomatous cells which produces a variable amount of osteoid bone. It arises centrally within the bone and can be subdivided into osteoblastic, chondroblastic and fibroblastic subtype, depending on the predominant cell type. : Radiographically, these tumors display a spectrum of bone changes from well-demarcated borders to lytic bone destruction with indefinite margins and variable cortical bone erosion or, in some cases, images of sclerotic bone. Therapeutic options for OSJ include surgery, chemotherapy and radiotherapy, which are employed according to age of the patient, histological classification and localization of the tumor. Today there is no a general consensus in the treatment guidelines for the OSJ though surgery represents the key of the treatment. The main prognostic factor deeply influencing the patient's prognosis remains the complete tumor resection with negative surgical margins. : The aim of the present review is to describe the state of the art regarding diagnostic and surgical treatment aspects of the primary osteosarcoma of the jaws.


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