Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or VSports app下载. mil. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely V体育官网. .

. 2010 Sep;62(9):2736-44.
doi: 10.1002/art.27582.

Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice

Lin Xu  1 , Jacqueline Servais, Ilona Polur, Doil Kim, Peter L Lee, Kimberly Chung, Yefu Li
Affiliations

Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice (V体育官网入口)

Lin Xu et al. Arthritis Rheum. 2010 Sep.

Abstract

Objective: To investigate whether the reduction of discoidin domain receptor 2 (DDR-2), a cell membrane tyrosine kinase receptor for native type II collagen, attenuates the progression of articular cartilage degeneration in mouse models of osteoarthritis (OA) VSports手机版. .

Methods: Double-heterozygous (type XI collagen-deficient [Col11a1(+/-)] and Ddr2-deficient [Ddr2(+/-)]) mutant mice were generated. Knee joints of Ddr2(+/-) mice were subjected to microsurgical destabilization of the medial meniscus. Conditions of the articular cartilage from the knee joints of the double-heterozygous mutant and surgically treated mice were examined by histology, evaluated using a modified Mankin scoring system, and characterized by immunohistochemistry V体育安卓版. .

Results: The rate of progressive degeneration in knee joints was dramatically reduced in the double-heterozygous mutant mice compared with that in the type XI collagen-deficient mice. The progression in the double-heterozygous mutant mice was delayed by ∼6 months. Following surgical destabilization of the medial meniscus, the progressive degeneration toward OA was dramatically delayed in the Ddr2(+/-) mice compared with that in their wild-type littermates. The articular cartilage damage present in the knee joints of the mice was directly correlated with the expression profiles of DDR-2 and matrix metalloproteinase 13 V体育ios版. .

Conclusion: Reduction of DDR-2 expression attenuates the articular cartilage degeneration of knee joints induced either by type XI collagen deficiency or by surgical destabilization of the medial meniscus VSports最新版本. .

PubMed Disclaimer

Figures

Figure 1
Figure 1. Histology of the articular cartilage of knee joints from double-heterozygous (cho/+ and Ddr2+/−) mice, cho/+ mice and their wild-type littermates
Each image shown is one representative section selected from 96 sections of an experimental group (12 sections from each knee joint and 8 knee joints in each experimental group). The representative section was selected based on the average score from the each experimental group. There were no obvious morphological differences in knee joint degeneration among the double-heterozygous mutant mice, cho/+ mice and their wild-type littermates at 3 months old. However, the degenerative condition of the articular cartilage in the cho/+ mice was far more advanced when compared with that of their wild-type littermates in each of the age groups - 6, 9 and 15 months old. The degenerative process was also observed in the double-heterozygous mutant mice with increasing age, but the rate of progression was dramatically reduced in the double-heterozygous mutant mice compared with that in cho/+ mice. (Bar=100 μm).
Figure 2
Figure 2. Average modified Mankin scores of double-heterozygous mutant mice, cho/+ mice and their wild-type littermates
The morphologic condition of the articular cartilage from the knee joints was evaluated. An average score representing 8 animals from each experimental group was obtained. A statistical comparison of the scores using the Mann-Whitney U-test indicated a significant difference among the groups at each age and the P value was less than 0.001 (see *). We found that the degenerative progression in the double-heterozygous mutant mice was delayed by approximately 6 months. Interestingly, the scores of the double-heterozygous mutant and cho/+ mice were similar at the age of 3 months old.
Figure 3
Figure 3. Expressions of Ddr2 and Mmp13 in knee joints of mice at the age of 6 months old
Each image (see panel A) is one representative section selected from 32 sections of an experimental group (8 sections from each knee and 4 knees in each group). More reddish-brown staining cells (Ddr2 or Mmp13 positive) were observed in the superficial layer of the cho/+ mice. In the double-heterozygous mutant mice, there were less Ddr2 or Mmp13 positive cells. There were hardly any positively staining cells detected in wild-type littermates at the age of 6 months and any of the three groups at the 3 months of age (data not shown). (Bar = 50 μm). The percentage of the positive staining cells in knees of mice at the age of 6 months old was obtained (see panel B). There were 23% of Ddr2 positive cells and 21% of Mmp13 positive cells in cho/+ mice and 13% of Ddr2 positive cells and 11% of Mmp13 positive cells in the double-heterozygous mutant mice. There were significant differences between two groups, p<0.05 (t-test). There were hardly Ddr2 positive and Mmp13 positive cells detected in wild-type littermates.
Figure 4
Figure 4. Histology of the articular cartilage of knee joints from mice following microsurgery
In the wild-type littermates, at 4 weeks following surgery, regional reduced Safranine O staining (see the arrow) was observed. At 8 weeks following surgery, fibrillation was seen (see the arrow). At 12 weeks following surgery, the articular cartilage appears thinner and the fibrillation extends to the deep layer of the cartilage. At 16 weeks following surgery, a complete loss of articular cartilage was evident. A delay of the degenerative process was seen in the Ddr2+/− mice following surgery. A mild degradation of proteoglycans was also seen in the knee joints of sham-surgery mice with aging. (Bar=100 μm).
Figure 5
Figure 5. Average modified Mankin scores of mice with the DMM microsurgery
To evaluate the morphologic condition of the articular cartilage of knee joints, an average score representing 8 animals from each group at each time point was obtained. A statistical comparison of the scores using the Mann-Whitney U-test indicated a significant difference between the two groups at each time point and the P value was less than 0.001 (see *). As the length of time following the surgery increased, the modified Mankin scores also increased, significantly, in the wild-type littermates with DMM surgery. However, the scores were not as dramatically increased in the Ddr2+/− mice with DMM surgery, particularly after 8 weeks post-surgery.
Figure 6
Figure 6. Expressions of Ddr2 and Mmp-13 in knee joints of mice at 4 weeks following the surgery
Each image (see panel A) shown is one representative section selected from 32 sections of an experimental group (8 sections from each knee joint and 4 knee joints in each experimental group). The representative section was selected based upon the percentage of positively staining cells in the section. More reddish-brown staining cells (Ddr2 or Mmp13 positive) were observed in the superficial layer of the wild-type littermates, compared with that of Ddr2+/− mice, following surgery. (Bar = 50 μm) The percentage of positive staining cells in knee joints of mice at 4 weeks following the surgery was obtained (see panel B). There were 19% of Ddr2 positive cells and 21% of Mmp13 positive cells in wild-type mice with DMM surgery and 11% of Ddr2 positive cells and 8% of Mmp13 positive staining cells in Ddr2+/− mice with DMM surgery. There were significant differences in the number of the positive cells between two groups, p<0.05 (t-test). There were hardly Ddr2 positive and Mmp13 positive cells detected in sham-surgery mice.
See this image and copyright information in PMC

"VSports app下载" References

    1. Hamerman D. The biology of osteoarthritis. The New England J Med. 1989;320:1322–30. - PubMed
    1. Goldring MB. Update on the biology of the chondrocyte and new approaches to treating cartilage diseases. Best Pract Res Clin Rheumatol. 2006;20:1003–25. - PubMed
    1. Stickens D, Behonick DJ, Ortega N, Heyer B, Hartenstein B, Yu Y, et al. Altered endochondral bone development in matrix metalloproteinase 13-deficient mice. Development. 2004;131:5883–95. - PMC - PubMed
    1. Mitchell PG, Magna HA, Reeves LM, Lopresti-Morrow LL, Yocum SA, Rosner PJ, et al. Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. J Clin Invest. 1996;97(3):761–8. - "V体育2025版" PMC - PubMed
    1. Reboul P, Pelletier JP, Tardif G, Cloutier JM, Martel-Pelletier J. The new collagenase, collagenase-3, is expressed and synthesized by human chondrocytes but not by synoviocytes. A role in osteoarthritis. J Clin Invest. 1996;97:2011–19. - PMC - PubMed

Publication types

"VSports手机版" MeSH terms

Substances (VSports注册入口)