Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β through the NF‐κB and MAPK pathways in rheumatoid arthritis

Zheng, Wenxin; R, Li; Pan, Heng; He, Dongyi; Xu, Rong; Guo, Taylor B.; Guo, Yajun; Zhang, Jingwu Z.

doi:10.1002/art.24625

Cited by 79 publications

(66 citation statements)

References 41 publications

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“…27,28 It has been reported that OPN regulates MCP-1 expression through the NF-kappaB and MAPK pathways in rheumatoid arthritis. 29 Furthermore, the fact that there is no difference in the ability of the three OPN transcripts to regulate MCP-1 and TGF-b1 suggests that OPN transcripts may regulate both cytokines through the common receptor binding domain. The data that OPN transcripts regulate MCP-1 via CD44 (a common receptor present in all OPN transcripts) further support our hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin splice variants expressed by breast tumors regulate monocyte activation via MCP-1 and TGF-β1

Sun¹,

Feng²,

Chen³

et al. 2013

Cell Mol Immunol

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Osteopontin (OPN), a multifunctional glycoprotein, has three transcripts that have distinct roles in tumors in vitro. Whether OPN transcripts have different functions in tumor processes in vivo is unclear. It has been reported that immune cell-derived OPN can promote tumor formation. We propose a hypothesis that tumor-derived OPN may facilitate tumor immune escape by affecting immune cell differentiation and function. In this study, we constructed lentiviral expression vectors of OPN transcripts and transfected them into the MCF-7 cell line. MCF-7 cells transfected with OPN transcripts were injected into the armpit of nude mice, and tumor growth was monitored. The results showed that all OPN transcripts promoted local tumor formation, but that there was no significant difference among transcripts. We also investigated the effect of the OPN expressed by tumor cells on monocyte differentiation by coculturing monocytes with tumor supernatant. We found OPN-c upregulated CD163 levels compared with OPN-a and OPN-b; however, none of the transcripts affected HLA-DR and CD206 levels. All OPN transcripts significantly inhibited TNF-a and enhanced IL-10 production by monocytes. Furthermore, we found that the overexpression of OPN transcripts significantly upregulated TGF-b1 and MCP-1 production by tumor cells. Using neutralizing antibody and recombinant cytokines, we found that OPN overexpressed by tumor cells regulates the production of TNF-a and IL-10 by monocytes partly via MCP-1 and TGF-b1, respectively. Collectively, our results show that OPN transcripts have no distinct role in breast cancer formation in vivo. We also demonstrate that OPN regulates the alternative activation of monocytes via TGF-b1 and MCP-1, which may represent an additional mechanism for tumor immune escape.

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Section: Discussionmentioning

confidence: 99%

Osteopontin splice variants expressed by breast tumors regulate monocyte activation via MCP-1 and TGF-β1

Sun¹,

Feng²,

Chen³

et al. 2013

Cell Mol Immunol

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“…5 Osteopontin (also known as secreted phosphoprotein 1, SPP1), an adhesive glycophosphoprotein widely expressed in tissues, body fluids, and cells under normal conditions, regulates physiologic processes such as development, differentiation, inflammation, and wound healing. [6][7][8][9] In addition, SPP1 is highly expressed in the microenvironment of various tumors, both by malignant and host cells. [10][11][12] Osteopontin has been linked with enhanced tumor progression and metastasis by modulating cell-cell interactions, by activating signal transduction pathways, by altering gene expression, and by promoting tumor cell survival.…”

Section: Introductionmentioning

confidence: 99%

Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis

et al. 2016

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The lungs are ubiquitous receptacles of metastases originating from various bodily tumors. Although osteopontin (SPP1) has been associated with tumor dissemination, the role of its isoforms in lung-directed metastasis is incompletely understood. We employed syngeneic mouse models of spontaneous and induced lung-targeted metastasis in C57BL/6 mice competent and deficient in both Spp1 alleles. Tumorderived osteopontin expression was modulated using either stable anti-Spp1 RNA interference, or forced overexpression of intracellular and secreted Spp1 isoforms. Identified osteopontin's downstream partners were validated using lung adenocarcinoma cells conditionally lacking the Trp53 gene and Ccr2-deficient mice. We determined that host-derived osteopontin was dispensable for pulmonary colonization by different tumor types. Oppositely, tumor-originated intracellular osteopontin promoted tumor cell survival by preventing tumor-related protein 53-mediated apoptosis, while the secretory osteopontin functioned in a paracrine mode to accelerate lung metastasis by enhancing tumor-derived C-C-motif chemokine ligand 2 signaling to cognate host receptors. As new ways to target osteopontin signaling are becoming available, the cytokine may constitute an important therapeutic target against pulmonary involvement by cancers of other organs. KEYWORDSC-C-motif chemokine ligand 2; inflammation and cancer; secreted phosphoprotein 1; spontaneous lung metastasis; tumor-related protein 53

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“…OPN is an important mediator of the immune response as it is involved in cell migration and Th1-mediated immunity (7,8). OPN was found to selectively induce expression of proinflammatory chemokines and acted as a crucial mediator in the rheumatoid synovium (9,10). Accumulating evidence suggests that higher OPN levels could be observed in the synovial fluid and synovial membrane in RA patients (11,12).…”

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confidence: 99%

Osteopontin Promotes Oncostatin M Production in Human Osteoblasts: Implication of Rheumatoid Arthritis Therapy

Chiang

Huang

et al. 2015

The Journal of Immunology

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Accumulating evidence indicates that subchondral bone might play an essential role in rheumatoid arthritis (RA). Osteopontin (OPN) induces the production of an important proinflammatory cytokine involved in the pathogenesis of RA. This study evaluated the activation of oncostatin M (OSM) by OPN in human primary osteoblasts to understand RA pathogenesis and characterized the intracellular signaling pathways involved in this activation. Quantitative PCR, ELISA, and Western blot results indicated that stimulation of human primary osteoblasts with OPN induces OSM expression through αvβ3 integrin/c-Src/platelet-derived growth factor receptor transactivation/MEK/ERK. Treatment of osteoblasts with OPN also increased c-Jun phosphorylation, AP-1 luciferase activity, and c-Jun binding to the AP-1 element on the OSM promoter, as demonstrated using chromatin immunoprecipitation assay. Moreover, inhibition of OPN expression using lentiviral-OPN short hairpin RNA resulted in the amelioration of articular swelling, cartilage erosion, and OSM expression in the ankle joint of mice with collagen-induced arthritis as shown using microcomputed tomography and immunohistochemistry staining. Our results imply that OSM expression in osteoblasts increases in response to OPN-induced inflammation in vitro. Finally, lentiviral-OPN short hairpin RNA ameliorates the inflammatory response and bone destruction in mice with collagen-induced arthritis. Therefore, OPN may be a potential therapeutic target for RA.

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Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β through the NF‐κB and MAPK pathways in rheumatoid arthritis

Cited by 79 publications

References 41 publications

Osteopontin splice variants expressed by breast tumors regulate monocyte activation via MCP-1 and TGF-β1

Osteopontin splice variants expressed by breast tumors regulate monocyte activation via MCP-1 and TGF-β1

Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis

Osteopontin Promotes Oncostatin M Production in Human Osteoblasts: Implication of Rheumatoid Arthritis Therapy

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