Murine Oncostatin M Stimulates Mouse Synovial Fibroblasts in Vitro and Induces Inflammation and Destruction in Mouse Joints in Vivo

Langdon, Carrie M.; Kerr, Christine; Hassen, Mohammed; Hara, Takahiko; Arsenault, A. Larry; Richards, Carl D.

doi:10.1016/s0002-9440(10)64634-2

Cited by 105 publications

(107 citation statements)

References 58 publications

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“…For example, local over-expression of OSM in the mouse knee joint induces changes to the joint that resemble OA, including cartilage destruction and periosteal bone formation similar to osteophytes (98,99). OSM also induces proteoglycan loss and cartilage damage ex-vivo (97,100).…”

Section: Osteoarthritismentioning

confidence: 99%

GP130 cytokines and bone remodelling in health and disease

Sims¹,

Walsh²

2010

BMB Reports

108

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Gp130 cytokinesGlycoprotein 130 (gp130) is a receptor subunit capable of intracellular signalling that is required for the cellular action of a wide range of cytokines. The most well known of these are interleukin (IL-) 6 and IL-11, leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF). Every cytokine that binds to gp130 generates specific intracellular signalling events by forming specific receptor:ligand complexes, each with distinct components and/or architecture (Fig.

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Section: Osteoarthritismentioning

confidence: 99%

GP130 cytokines and bone remodelling in health and disease

Sims¹,

Walsh²

2010

BMB Reports

108

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“…A common theme in connective tissue remodeling and homeostasis is the balance between the actions of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). Oncostatin M has a prominent role in the regulation of connective tissue extracellular matrix (ECM) through regulation of MMPs and TIMPs (8)(9)(10)(11)(12). Utilizing an adenoviral vector (Ad) overexpression system, we previously demonstrated that transient ectopic expression of mouse (m)OSM (AdmOSM) in the lungs of mice leads to ECM accumulation (13,14).…”

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confidence: 99%

A Mouse Model of Airway Disease: Oncostatin M-Induced Pulmonary Eosinophilia, Goblet Cell Hyperplasia, and Airway Hyperresponsiveness Are STAT6 Dependent, and Interstitial Pulmonary Fibrosis Is STAT6 Independent

Fritz

Kerr

Fattouh

et al. 2011

The Journal of Immunology

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Oncostatin M (OSM), a pleiotropic cytokine of the gp130 cytokine family, has been implicated in chronic allergic inflammatory and fibrotic disease states associated with tissue eosinophilia. Mouse (m)OSM induces airway eosinophilic inflammation and interstitial pulmonary fibrosis in vivo and regulates STAT6 activation in vitro. To determine the requirement of STAT6 in OSM-induced effects in vivo, we examined wild-type (WT) and STAT6-knockout (STAT6−/−) C57BL/6 mouse lung responses to transient ectopic overexpression of mOSM using an adenoviral vector (AdmOSM). Intratracheal AdmOSM elicited persistent eosinophilic lung inflammation that was abolished in STAT6−/− mice. AdmOSM also induced pronounced pulmonary remodeling characterized by goblet cell hyperplasia and parenchymal interstitial fibrosis. Goblet cell hyperplasia was STAT6 dependent; however, parenchymal interstitial fibrosis was not. OSM also induced airway hyperresponsiveness in WT mice that was abolished in STAT6−/− mice. OSM stimulated an inflammatory signature in the lungs of WT mice that demonstrated STAT6-dependent regulation of Th2 cytokines (IL-4, IL-13), chemokines (eotaxin-1/2, MCP-1, keratinocyte chemoattractant), and extracellular matrix modulators (tissue inhibitor of matrix metalloproteinase-1, matrix metalloproteinase-13), but STAT6-independent regulation of IL-4Rα, total lung collagen, collagen-1A1, -1A2 mRNA, and parenchymal collagen and α smooth muscle actin accumulation. Thus, overexpression of mOSM induces STAT6-dependent pulmonary eosinophilia, mucous/goblet cell hyperplasia, and airway hyperresponsiveness but STAT6-independent mechanisms of lung tissue extracellular matrix accumulation. These results also suggest that eosinophil or neutrophil accumulation in mouse lungs is not required for OSM-induced lung parenchymal collagen deposition and that OSM may have unique roles in the pathogenesis of allergic and fibrotic lung disease.

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“…Intraarticular overexpression of OSM in transgenic mice causes joint inflammation and cartilage destruction (15,16). Furthermore, the relevance of OSM in arthritis was shown in a murine model in which application of antibodies to OSM ameliorated arthritis (17).…”

mentioning

confidence: 99%

Induction of CCL13 expression in synovial fibroblasts highlights a significant role of oncostatin M in rheumatoid arthritis

Hintzen¹,

Quaiser²,

Pap³

et al. 2009

Arthritis & Rheumatism

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Objective. To investigate the molecular mechanisms of CCL13/monocyte chemoattractant protein 4 (MCP-4) chemokine expression through proinflammatory cytokines in different primary human fibroblasts and the contribution of CCL13 to monocyte migration.Methods. Using RNase protection assays and enzyme-linked immunosorbent assays, we quantified the expression of CCL13 compared with that of CCL2/ MCP-1 in primary human fibroblasts. Boyden chamber assays were performed to determine the importance of CCL13 for migration of primary monocytes. Pharmacologic inhibitors as well as small interfering RNA knockdown approaches were used to investigate the signaling pathways regulating CCL13 expression.Results. The interleukin-6 (IL-6)-type cytokine oncostatin M (OSM) was a powerful inducer of CCL13 expression in primary synovial fibroblasts from patients with rheumatoid arthritis (RA) as well as those from healthy control subjects but not in other types of fibroblasts. Neither IL-6 nor tumor necrosis factor ␣ could stimulate the expression of CCL13 in synovial fibroblasts; IL-1␤ was a very weak inducer. Synovial fibroblasts from patients with RA constitutively produced low amounts of CCL13, which was partially dependent on constitutive production of OSM. By investigating the underlying molecular mechanism, we identified STAT-5, ERK-1/2, and p38 as critical factors involved in OSM-dependent transcription and messenger RNA stabilization of CCL13.Conclusion. In contrast to other prominent cytokines involved in the pathogenesis of RA, OSM can strongly up-regulate the expression of CCL13, a chemokine recently identified in the synovial fluid of patients with RA. Despite potent OSM-induced signal transduction in all types of fibroblasts analyzed, only synovial fibroblasts secreted CCL13, which might be indicative of tissue-specific imprinting of different fibroblasts during development.

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Murine Oncostatin M Stimulates Mouse Synovial Fibroblasts in Vitro and Induces Inflammation and Destruction in Mouse Joints in Vivo

Cited by 105 publications

References 58 publications

GP130 cytokines and bone remodelling in health and disease

GP130 cytokines and bone remodelling in health and disease

A Mouse Model of Airway Disease: Oncostatin M-Induced Pulmonary Eosinophilia, Goblet Cell Hyperplasia, and Airway Hyperresponsiveness Are STAT6 Dependent, and Interstitial Pulmonary Fibrosis Is STAT6 Independent

Induction of CCL13 expression in synovial fibroblasts highlights a significant role of oncostatin M in rheumatoid arthritis

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