Transgenic mice over-expressing carbonic anhydrase I showed aggravated joint inflammation and tissue destruction

BMC Musculoskeletal Disorders

Xiaotian Chang³  Hengwei Xu²  Wei Zhang¹  Lin Wang⁴  Yabing Zheng⁴ 

[1] The Secondary People’s Hospital of Jinan, Jingyi road 148, Jinan, Shandong, 250001, P. R. China;Department of Pharmacy, Shandong Provincial Tumor Hospital, Jiyan road 440, Jinan, Shandong 250117, P. R. China;Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong University, Jingshi road 16766, Jinan, Shandong 250014, P. R. China;Research Center for Medical Biotechnology, Shandong Academy of Medical Sciences, Jingshi road 18877, Jinan, Shandong 250062, P. R. China

关键词: Rheumatoid arthritis (RA);    Ankylosing spondylitis (AS);    collagen-induced arthritis (CIA);    Transgenic mice;    New bone formation;    Carbonic anhydrase I (CA1);   

Others  :  1134328
DOI  :  10.1186/1471-2474-13-256

 received in 2012-07-21, accepted in 2012-12-17,  发布年份 2012

【 摘 要 】

Background

Studies have demonstrated that carbonic anhydrase I (CA1) stimulates calcium salt precipitation and cell calcification, which is an essential step in new bone formation. Our study had reported that CA1 encoding gene has a strong association with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), two rheumatic diseases with abnormal new bone formation and bone resorption in joints. This study investigated the effect of CA1 on joint inflammation and tissue destruction in transgenic mice that over-express CA1 (CA1-Tg).

Methods

CA1-Tg was generated with C57BL/6J mice by conventional methods. CA1-Tg was treated with collagen-II to induce arthritis (CIA). Wild-type mice, CA1-Tg treated with bovine serum albumin (BSA) and transgenic mice over-expressing PADI4 (PADI4-Tg), a gene known to be involved in rheumatoid arthritis, were used as controls. Histochemistry and X-ray radiographic assay were used to examine joint destruction. Western blotting and real time-PCR were used to examine CA1 expression.

Results

CIA was observed in 60% of CA1-Tg, 20% of PADI4-Tg and 20% of wild-type mice after collagen injections. No CIA was found in CA1-Tg mice that received injections of BSA. The arthritic score was 5.5 ± 0.84 in the CA1-Tgs but the score was less than 2 in the injected wild-type mice and the PADI4-Tgs. The thickness of the hind paws in the CA1-Tgs was 3.46 ± 0.11 mm, which was thicker than that of PADI4-Tgs (2.23 ± 0.08 mm), wild-type mice (2.08 ± 0.06 mm) and BSA-treated CA1-Tgs (2.04 ± 0.07 mm). Histochemistry showed obvious inflammation, synovial hyperplasia and bone destruction in the joints of CA1-Tg that was not detected in PADI4-Tgs or wild-type mice. X-ray assays showed bone fusion in the paws and spines of CA1-Tg mice.

Conclusion

Over-expression of CA1 may aggravate joint inflammation and tissue destruction in the transgenic mice.

【 授权许可】

   
2012 Zheng et al.; licensee BioMed Central Ltd.

【 图 表 】

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