Role of osteopontin in amplification and perpetuation of rheumatoid synovitis

Xu, Guangwu; Nie, Hong; Li, Ningli; Zheng, Wenxin; Zhang, Dongqing; Gao, Feng; Ni, Lei; Xu, Rong; Hong, Jian; Zhang, Jingwu Z.

doi:10.1172/jci200523273

Cited by 123 publications

(44 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Analogous to macrophages of adipose tissue in obesity and synovial T cells in rheumatoid synovitis, the overexpression of OPN in psoriasis seems to be correlated to disease severity only in the skin, as suggested by previous studies. The confined reduction of local OPN after systemic therapies or phototherapy may reflect an indirect rather than direct effect of the therapy on OPN levels, once OPN is not proportionally reduced with the decrease of PASI score [28,37,44]. Since OPN plasma levels were also reduced after therapy with adalimumab or etanercept [45], further studies addressing OPN levels in non-responder patients treated with anti-TNF-a are necessary to investigate its importance as an alternative inflammatory pathway in psoriasis.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin, CCL5 and CXCL9 are independently associated with psoriasis, regardless of the presence of obesity

et al. 2015

View full text Add to dashboard Cite

Psoriasis is an autoimmune disease associated with the production of pro-inflammatory cytokines. The identification of these molecules in the pathogenesis of psoriasis facilitated the use of monoclonal antibodies to block their actions as a treatment for severe psoriasis. An increased inflammatory response has been documented in patients with obesity, a condition that is associated with the occurrence and severity of psoriasis. Osteopontin (OPN), TNF and CXCL9 levels are enhanced in patients with psoriasis, although OPN has been documented in the adipose tissue of obese patients without psoriasis. The prevalence of obesity is much higher in psoriasis patients compared with the general population. Thus, we aimed to evaluate the relationship between cytokine levels and psoriasis in the context of obesity. We compared OPN and CXCL9 plasma levels among 117 psoriasis patients and 27 healthy body mass index-matched subjects using ELISA. We also analyzed the TNF, CCL2 and CCL5 levels in a smaller subgroup of patients and matched controls. Median OPN, CCL5 and CXCL9 levels were significantly higher in psoriasis patients compared with the controls, independent of obesity. There was no difference between the median CCL2 levels in the psoriasis patients and the controls (P<0.05), although the CCL2 levels were elevated in obese patients compared with non-obese psoriasis patients (P<0.001). Facial involvement and the psoriasis area severity index (PASI) score were not associated (P<0.05) with OPN levels or elevated levels of chemokines. There was no significant correlation between the OPN and CXCL9 levels or the OPN and TNF levels in psoriasis patients. This work confirms that OPN, CCL5 and CXCL9 plasma levels are higher in psoriasis patients and provides evidence that their higher levels are not a consequence of obesity. Furthermore, the results demonstrate that OPN production is independent of TNF-α and CXCL9.

show abstract

Section: Discussionmentioning

confidence: 99%

Osteopontin, CCL5 and CXCL9 are independently associated with psoriasis, regardless of the presence of obesity

et al. 2015

View full text Add to dashboard Cite

show abstract

“…A number of studies using OPN-deficient mouse models and OPN-neutralizing antibodies (Abs) have demonstrated the importance of OPN in the development of several inflammatory diseases, particularly those involving CD4 T helper 1 (Th1)-associated immune responses [2][3][4][5][6][7][8][9][10]. In humans, high levels of OPN have been observed in several diseases associated with Th1 responses, such as sarcoidosis [11], tuberculosis [11], rheumatoid arthritis [12], Crohn's disease [13], and multiple sclerosis (MS) [14]. However, the role of OPN in Th2-associated diseases, rather than diseases involving Th-1, remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Role of osteopontin, a multifunctional protein, in allergy and asthma

Konno

Kurokawa

Uede

et al. 2011

Clin Experimental Allergy

View full text Add to dashboard Cite

Osteopontin (OPN) is an extracellular matrix protein and immune modulator with a wide range of functions. OPN is recognized as a key cytokine in Th1 immune responses, yet its potential involvement in allergic/asthmatic responses has been investigated only recently. Current data from molecular and cellular studies and studies of OPN-deficient mice provide evidence that OPN plays multiple roles in the regulation of allergic responses, including regulation of IgE response, inflammatory cell migration, and the development of airway fibrosis and angiogenesis. These results suggest that OPN is a pleiotropic cytokine that functions both systemically and locally in tissue mucosa. Notably, OPN is able to exert its effects through different functional domains, and the secreted and intracellular forms of OPN may have distinct functions. Future research to elucidate all aspects of OPN function is needed to ultimately establish its role in the regulation of immune responses and various disease processes, including those critically involved in the development of allergies and asthma.

show abstract

“…The OPN molecule contains a classical cell-binding domain of arginine, glycine, and aspartic acid (RGD) recognized by integrins such as ␣ v ␤ 3 and ␣ 5 ␤ 1 , and an additional cell-binding domain (serine, valine, valine, tyrosine, glycine, lysine, and arginine [SVVYGLR] in humans and serine, lysine, alanine, tyrosine, glycine, lysine, and arginine [SLAYGLR] in mice) that is recognized by ␣ 4 ␤ 1 and ␣ 9 ␤ 1 (Denhardt and Guo, 1993;Yokosaki et al, 1999). OPN has been implicated in the pathogenesis of various intractable inflammatory diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), inflammatory bowel disease, atherosclerosis, inflammatory ocular disease, and allergic airway disease (Chabas et al, 2001;Bruemmer et al, 2003;Matsui et al, 2003;Yamamoto et al, 2003;Diao et al, 2004;Sato et al, 2005;Xu et al, 2005;Hur et al, 2007;Kitamura et al, 2007;Xanthou et al, 2007). Importantly, each of these disorders is associated with high tissue and plasma OPN expression.…”

Section: Introductionmentioning

confidence: 99%

Osteopontin Small Interfering RNA Protects Mice from Fulminant Hepatitis

et al. 2007

View full text Add to dashboard Cite

Osteopontin (OPN) has been implicated in various helper T cell type 1 immunity-mediated diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), Crohn's disease, and fulminant hepatitis. Increased expression of OPN has been detected in pathological foci of these diseases. RA and fulminant hepatitis have been successfully treated by administration of neutralizing anti-OPN antibody in mice. Antibody treatment may elicit side effects including allergic reactions against heterologous antibody proteins, thus necessitating humanization of antibody. To provide alternative means to neutralize OPN function, in this study we explored the possibility of using OPN small interfering RNA (siRNA) to silence OPN gene expression. In vitro, OPN siRNA efficiently silenced the expression of both exogenous and endogenous OPN gene. After hydrodynamic intravenous injection of OPN siRNA, OPN siRNA was efficiently delivered to the liver, which resulted in the efficient silencing of OPN gene expression in liver. In a murine model of concanavalin A (ConA)-induced fulminant hepatitis, OPN expression was elevated in liver and severe hepatic necrosis was induced. Importantly, after OPN siRNA treatment, the OPN expression level in liver was significantly reduced and liver tissue injury was ameliorated, as reflected by the significant reduction of serum alanine aminotransferase levels and almost normal liver histology. Thus, this study indicates that OPN siRNA delivery has therapeutic potential in various inflammatory diseases in which OPN play a critical role by silencing OPN gene expression in vivo.

show abstract

Role of osteopontin in amplification and perpetuation of rheumatoid synovitis

Cited by 123 publications

References 26 publications

Osteopontin, CCL5 and CXCL9 are independently associated with psoriasis, regardless of the presence of obesity

Osteopontin, CCL5 and CXCL9 are independently associated with psoriasis, regardless of the presence of obesity

Role of osteopontin, a multifunctional protein, in allergy and asthma

Osteopontin Small Interfering RNA Protects Mice from Fulminant Hepatitis

Contact Info

Product

Resources

About