Dataset Information

Macrophage migration inhibitory factor activates the inflammatory response in joint capsule fibroblasts following post-traumatic joint contracture.

ABSTRACT:

Objectives

Joint capsule fibrosis caused by excessive inflammation leading to post-traumatic joint contracture (PTJC). Fibroblasts trigger inflammation under the challenge of various proinflammatory cytokines. Macrophage migration inhibitory factor (MIF) is a prominent proinflammatory cytokine involved in inflammation- and fibrosis-associated pathophysiology, we investigated the role of MIF in PTJC.

Methods

Using rat PTJC model and fibroblast inflammation model, we detected MIF expression in posterior joint capsule. Primary joint capsule fibroblasts (JFs) were used to investigate the effects of MIF on cell proliferation, migration and proinflammatory cytokines production. The mechanism of JF-mediated events was evaluated by qRT-PCR, western blot and immunoprecipitation. We screened the mRNA expression profile to identify gene candidates that mediate the effect of MIF on JFs.

Results

MIF increased in posterior joint capsule following PTJC and co-localized with fibroblasts. Injection of MIF inhibitor significantly suppressed joint capsule inflammation and fibrosis. In vitro, MIF promoted JF proliferation, migration, and inflammation by regulating mitogen-activated protein kinase/nuclear factor-κB pathway through coupling with CD74. Transcriptome analysis revealed that lipid metabolism-related factors Pla2g2a, Angptl4, and Sgpp2, downstream of MIF/CD74, were potentially implicated in JF inflammation.

Conclusion

MIF/CD74 axis elicited JF inflammation and may provide new therapeutic targets for joint capsule fibrosis in PTJC.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7950233 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Macrophage migration inhibitory factor activates the inflammatory response in joint capsule fibroblasts following post-traumatic joint contracture.

Zhang Yuxin Y Lu Shenji S Fan Shuai S Xu Lili L Jiang Xin X Wang Kexin K Cai Bin B

Aging 20210217 4

<h4>Objectives</h4>Joint capsule fibrosis caused by excessive inflammation leading to post-traumatic joint contracture (PTJC). Fibroblasts trigger inflammation under the challenge of various proinflammatory cytokines. Macrophage migration inhibitory factor (MIF) is a prominent proinflammatory cytokine involved in inflammation- and fibrosis-associated pathophysiology, we investigated the role of MIF in PTJC.<h4>Methods</h4>Using rat PTJC model and fibroblast inflammation model, we detected MIF ex ...[more]

PMID: 33601337

Similar Datasets

Project description:Elbow trauma can lead to post-traumatic joint contracture (PTJC), which is characterized by loss of motion associated with capsule/ligament fibrosis and cartilage damage. Unfortunately, current therapies are often unsuccessful or cause complications. This study aimed to determine the effects of prophylactically administered simvastatin (SV) and losartan (LS) in two preclinical models of elbow PTJC: an in vivo elbow-specific rat injury model and an in vitro collagen gel contraction assay. The in vivo elbow rat (n = 3-10/group) injury model evaluated the effects of orally administered SV and LS at two dosing strategies [i.e., low dose/high frequency/short duration (D1) vs. high dose/low frequency/long duration (D2)] on post-mortem elbow range of motion (via biomechanical testing) as well as capsule fibrosis and cartilage damage (via histopathology). The in vitro gel contraction assay coupled with live/dead staining (n = 3-19/group) evaluated the effects of SV and LS at various concentrations (i.e., 1, 10, 100 µM) and durations (i.e., continuous, short, or delayed) on the contractibility and viability of fibroblasts/myofibroblasts [i.e., NIH3T3 fibroblasts with endogenous transforming growth factor-beta 1 (TGFβ1)]. In vivo, no drug strategy prevented elbow contracture biomechanically. Histologically, only SV-D2 modestly reduced capsule fibrosis but maintained elevated cellularity and tissue hypertrophy, and both SV strategies lessened cartilage damage. SV modest benefits were localized to the anterior region, not the posterior, of the joint. Neither LS strategy had meaningful benefits in capsule nor cartilage. In vitro, irrespective of the presence of TGFβ1, SV (≥10 μM) prevented gel contraction partly by decreasing cell viability (100 μM). In contrast, LS did not prevent gel contraction or affect cell viability. This study demonstrates that SV, but not LS, might be suitable prophylactic drug therapy in two preclinical models of elbow PTJC. Results provide initial insight to guide future preclinical studies aimed at preventing or mitigating elbow PTJC.

Dataset Information

Macrophage migration inhibitory factor activates the inflammatory response in joint capsule fibroblasts following post-traumatic joint contracture.

Objectives

Methods

Results

Conclusion

Publications

Macrophage migration inhibitory factor activates the inflammatory response in joint capsule fibroblasts following post-traumatic joint contracture.

Similar Datasets

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