lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

Now published in The Lancet

Cortistatin Binds to TNF-α Receptors and Protects Against Osteoarthritis

48 Pages Posted: 8 Dec 2018

See all articles by Ruize Qu

Ruize Qu

Shandong University - Department of Pathology

Xiaomin Chen

Shandong University - Department of Pathology

Yuhua Li

Shandong University - Department of Pathology

Wenhan Wang

Shandong University - Cheeloo College of Medicine

Cheng Qiu

Shandong University - Cheeloo College of Medicine

Xin Pan

Shandong University - Department of Orthopedics

Liang Liu

University of South Australia - School of Pharmacy and Medical Sciences

Krasimir Vasilev

University of South Australia - School of Engineering; University of South Australia - Future Industries Institute

John Hayball

University of South Australia - School of Pharmacy and Medical Sciences

Shuli Dong

Shandong University

Weiwei Li

Shandong University - Department of Pathology

Yunpeng Zhao

Shandong University - Department of Orthopedics

More...

Abstract

Osteoarthritis (OA) is a common degenerative disease worldwide, and tumor necrosis factor (TNF-α) is known to play critical roles in OA. Cortistatin (CST) is a recently discovered neuropeptide that plays a vital role in inflammatory reactions. However, it is unknown whether CST is involved in cartilage degeneration and OA development. This study investigated the interaction between CST and TNF-α receptors, revealing that CST competitively bound to TNFR1 as well as TNFR2. In addition, primary chondrocyte experiments showed that CST suppressed the proinflammatory function of TNF-α. Moreover, both spontaneous and surgically induced OA models were established in wild-type and CSTknockout mice. Deficiency of CST led to an accelerated OA-like phenotype, while exogenous CST attenuated OA development in vivo, causing alterations of cartilage destruction and expression of degenerative biomarkers. Furthermore, TNFR1- and TNFR2-knockout mice were used for analysis and indicated that TNFRs might be involved in the protective role of CST in OA. Additionally, experiments in primary chondrocytes and NF-κB luciferase reporter gene mice revealed that CST inhibited activation of the NF-κB signaling pathway in OA. Overall, this study provides new insight into the pathogenesis and potential therapeutic targets for cartilage degenerative diseases, including OA.

Funding Statement: This work was supported by Key Research and Development Projects of Shandong Province (No. 2015GSF118115), the Natural Science Foundation of Shandong Province (BS2014YY048 and BS2015SW028 to Yunpeng Zhao, and ZR2016HM53 to Yuhua Li), the Cross-disciplinary Fund of Shandong University (Grant No. 26010178611010) and the National Natural Science Foundation of China (81501880 to Yunpeng Zhao and 81602761 to Weiwei Li).

Declaration of Interests: The authors have declared that no conflict of interest exists.

Ethics Approval Statement: All the experiments were agreed by the ethical review committee of Qilu Hospital, Shandong University, and additionally, the prior informed consent of the patients. Samples of human cartilage were collected from total knee joint replacement surgery patients for OA, with the detection of MOAKS, according to the agreement of the ethical review committee of Qilu Hospital, Shandong University, and the prior informed consent of the patients. All experiments were conducted in compliance with the relevant guidelines and regulations.

Keywords: osteoarthritis; chondrocyte; cortistatin; TNFR; NF-κB signaling

Suggested Citation

Qu, Ruize and Chen, Xiaomin and Li, Yuhua and Wang, Wenhan and Qiu, Cheng and Pan, Xin and Liu, Liang and Vasilev, Krasimir and Hayball, John and Dong, Shuli and Li, Weiwei and Zhao, Yunpeng, Cortistatin Binds to TNF-α Receptors and Protects Against Osteoarthritis (March 12, 2018). Available at SSRN: https://ssrn.com/abstract=3296645 or http://dx.doi.org/10.2139/ssrn.3296645

Ruize Qu

Shandong University - Department of Pathology

27 Shanda Nanlu
South Rd.
Jinan, Shandong 250100
China

Xiaomin Chen

Shandong University - Department of Pathology

27 Shanda Nanlu
South Rd.
Jinan, Shandong 250100
China

Yuhua Li

Shandong University - Department of Pathology

27 Shanda Nanlu
South Rd.
Jinan, Shandong 250100
China

Wenhan Wang

Shandong University - Cheeloo College of Medicine

Jinan
China

Cheng Qiu

Shandong University - Cheeloo College of Medicine

Jinan
China

Xin Pan

Shandong University - Department of Orthopedics

27 Shanda Nanlu
South Rd.
Jinan, Shandong 250100
China

Liang Liu

University of South Australia - School of Pharmacy and Medical Sciences

37-44 North Terrace, City West Campus
Adelaide, 5001
United States

Krasimir Vasilev

University of South Australia - School of Engineering ( email )

Level 1, building J
Mawson Lakes Campus
Mawson Lakes, South Australia 5095
Australia

University of South Australia - Future Industries Institute ( email )

Mawson Lakes, South Australia 5095
Australia

John Hayball

University of South Australia - School of Pharmacy and Medical Sciences

37-44 North Terrace, City West Campus
Adelaide, 5001
United States

Shuli Dong

Shandong University

27 Shanda Nanlu
South Rd.
Jinan, SD Shandong 250100
China

Weiwei Li

Shandong University - Department of Pathology ( email )

27 Shanda Nanlu
South Rd.
Jinan, Shandong 250100
China

Yunpeng Zhao (Contact Author)

Shandong University - Department of Orthopedics ( email )

27 Shanda Nanlu
South Rd.
Jinan, Shandong 250100
China