期刊
BMC MUSCULOSKELETAL DISORDERS
卷 13, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1471-2474-13-256
关键词
Carbonic anhydrase I (CA1); New bone formation; Transgenic mice; collagen-induced arthritis (CIA); Ankylosing spondylitis (AS); Rheumatoid arthritis (RA)
资金
- National Natural Science Foundation of China [NTFC 30972720]
- National Basic Research Program of China [2010CB529105]
- Shandong Taishan Scholarship
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.
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