Expression of hedgehog signal pathway in articular cartilage is associated with the severity of cartilage damage in rats with adjuvant-induced arthritis

Journal of Inflammation

Research

Li Cai¹  Ting-ni Wu²  Rong Li²  Jun Li²  Cheng-mu Hu² 

[1] Department of Pathology, School of Basic Medicine, Anhui Medical University, 81 Meishan Road, 230032, Hefei, Anhui, China;School of Pharmacy, Anhui Medical University, 81 Meishan Road, 230032, Hefei, Anhui, China;Key Laboratory for Bioactivity of Natural Medicine of Anhui Province, 230032, Hefei, Anhui, China;

关键词: Adjuvant-induced arthritis;    Articular cartilage;    Hedgehog signal pathway;    Inflammation;    Rheumatoid arthritis;   

DOI  :  10.1186/s12950-015-0072-5

 received in 2014-08-07, accepted in 2015-03-20,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundCartilage damage is a crucial step in rheumatoid arthritis (RA) disease progress while its molecular mechanisms are not fully understood. Here we investigated the expression of hedgehog (Hh) signal pathway in articular cartilage of adjuvant-induced arthritis (AIA) rats and its possible pathological role in cartilage damage.Methods30 rats were divided into sham and AIA group (n = 15). Complete Freund’s adjuvant was used to induce AIA. Secondary paw swelling was measured on day 10, 14, 18, 22 and 26 after induction. Rats were sacrificed on day 26 and knee joints and cartilage tissues were collected. Paw swelling, cartilage histopathologic changes and OARSI scores were used to evaluate AIA in rats. The protein expression of Hh signal related genes (Shh, Ptch1, Smo and Gli1) in cartilage were assayed by immunohistochemistry. The mRNA levels of Shh, Ptch1, Smo, Gli1, type-II collagen (COII) and aggrecan in cartilage were assayed by real-time PCR. In vitro study, cultured AIA chondrocytes were treated with cyclopamine (a specific inhibitor of Hh signal) and the mRNA levels of Hh signal and ECM components (COII and aggrecan) were measured by real-time PCR.ResultsImmunohistochemical results revealed that Shh, Ptch1, Smo and Gli1 proteins showed higher expression in the articular cartilage of AIA rats than those of sham rats. Real-time PCR results confirmed that Shh, Ptch1, Smo and Gli1 mRNA levels in cartilage tissues of AIA rats were significantly increased compared with those of sham rats (1.6, 1.4, 1.6, 2.0 fold, respectively). The mRNA levels of Shh, Ptch1, Smo, and Gli1 were associated with the severity of cartilage damage (indicated by OARSI scores, COII and aggrecan mRNA levels in cartilage). In vitro, cyclopamine effectively decreased the mRNA levels of Shh, Ptch1, Smo and Gli1, and increased the mRNA levels of COII and aggrecan in AIA chondrocytes, suggesting Hh signal inhibition might directly promote ECM production.ConclusionsOur findings present certain experimental evidence that Hh signal pathway is involved in the pathogenesis of cartilage damage in RA.

【 授权许可】

Unknown   
© Li et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.