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. 2016;2016:9529630.
doi: 10.1155/2016/9529630. Epub 2016 Apr 20.

Icariin Prevents Cartilage and Bone Degradation in Experimental Models of Arthritis

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Free PMC article

Icariin Prevents Cartilage and Bone Degradation in Experimental Models of Arthritis

Chen Chao Wei et al. Mediators Inflamm. .
Free PMC article

Abstract

Background: Icariin (ICA) is an active compound extracted from Epimedium brevicornum Maxim. Previous reports have shown that icariin has a clinically significant therapeutic effect on rheumatoid arthritis. However, little is known about the mechanism by which icariin inhibits cartilage and bone degradation.

Methods: New Zealand rabbits were immunized with antigen-induced arthritis (AIA) and treated with icariin. Joint tissues from rabbits were studied by histological analysis, transmission electron microscopy (TEM), and micro-CT. The expression levels of receptor activator of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) in joint tissues were determined using immunohistochemistry and real-time PCR analysis.

Results: Histological analysis and TEM sections of cartilage in the ICA treated group showed a low level of chondrocyte destruction. Micro-CT analysis showed that the bone mineral density value and bone structural level in ICA treated rabbits were significantly higher compared with those in the AIA group. Immunohistochemistry and real-time PCR analysis showed that icariin treatment reduced RANKL expression and enhanced OPG expression levels, as compared to the AIA group.

Conclusion: These data indicate that ICA suppresses articular bone loss and prevents joint destruction. This study also determined that ICA regulated articular bone loss in part by regulating RANKL and OPG expression.

Figures

Figure 1
Figure 1
Histological evaluation of rabbit knee joint cartilage stained with haematoxylin and eosin. (a) Normal group showing the chondrocytes were arranged in a straight line and located centrally within its lacunae. These chondrocytes showed centrally located nuclei, fine granular cytoplasm that contains few discrete vacuoles, and were surrounded by extracellular matrix. (b) AIA group: the chondrocytes (arrows) showed significant destruction along with pyknotic nuclei, no clear lacunae, and many vacuoles inside the lacunae. (c) ICA group showing destroyed chondrocytes (arrows). Nuclei were not centrally located and within a vacuole inside the lacunae. (d) Control group: the disrupted chondrocytes showed that many atrophic nuclei were not centrally located and some had no nuclei (arrows) (original magnification ×300). L, lacunae; N, nuclei; E, extracellular matrix; V, vacuoles. (e) The Mankin grading system was used for the evaluation of articular cartilage degeneration. In the AIA group, higher Mankin score values were obtained with increasing cartilage degeneration (p < 0.01). However, there was a lower mean score in the ICA group compared with that in the AIA group (p < 0.05). Results are presented as the mean ± SD. n = 6   p < 0.05, ∗∗ p < 0.01 versus corresponding group.
Figure 2
Figure 2
TEM micrographs of chondrocytes and numbers of organelles in chondrocytes were counted to evaluate chondrocytes degeneration. (a) Normal group, (b) AIA group, (c) ICA group, and (d) control group (×10,000 magnification). F, filopodia; G, Golgi; N, euchromatin nucleus; M, mitochondria; RER, rough endoplasmic reticulum. The numbers of mitochondria (e) and Golgi bodies (f) were significantly decreased in the AIA group compared with those in the normal group (p < 0.01), whereas the numbers of mitochondria and Golgi were greatly increased in the ICA group (p < 0.05). However, when compared with the AIA group, the levels present in the IND positive control rabbits did not attain statistical significance. Results are presented as mean ± SD. n = 6   p < 0.05, ∗∗ p < 0.01 versus corresponding group.
Figure 3
Figure 3
Effects of icariin on BMD and bone structural quality of rabbits measured by micro-CT. Representative μ-CT images of the distal femur (a). The BMD was significantly decreased in AIA rabbits as compared to the normal group rabbits. However, the BMD value in ICA treated rabbits was significantly higher compared with that in the AIA group and no change of BMD was found between the control group and the AIA group (b). There was a significant decrease in BV/TV (c), Tb.N (d), and Tb.Th (e) in the AIA rabbits as compared to the normal group. In addition there was a significant increase in Tb.Sp in the AIA group (f). Compared with AIA rabbits, the trabecular BV/TV (c), Tb.N (d), and Tb.Th (e) were significantly increased whereas the Tb.Sp (f) was significantly decreased in ICA treated rabbits. Results are presented as the mean ± SD. p < 0.05, ∗∗ p < 0.01 versus corresponding group.
Figure 4
Figure 4
Decreased RANKL and enhanced OPG expression in articular cartilage is associated with icariin therapy. Icariin treatment reduced RANKL and enhanced OPG protein and mRNA expression in subchondral bone as shown by immunohistochemistry (a) and real-time PCR analysis (b, c). RANKL/OPG ratio (d). Results are presented as the mean ± SD. p < 0.05, ∗∗ p < 0.01 versus corresponding group. Arrow heads indicate positive staining in subchondral bone. Original magnification, ×400.

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References

    1. Lesuis N., Befrits R., Nyberg F., van Vollenhoven R. F. Gender and the treatment of immune-mediated chronic inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease and psoriasis: an observational study. BMC Medicine. 2012;10, article 82 doi: 10.1186/1741-7015-10-82. - DOI - PMC - PubMed
    1. Adlowitz D. G., Barnard J., Biear J. N., et al. Expansion of activated peripheral blood memory B cells in rheumatoid arthritis, impact of B cell depletion therapy, and biomarkers of response. PLoS ONE. 2015;10(6) doi: 10.1371/journal.pone.0128269.e0128269 - DOI - PMC - PubMed
    1. Meednu N., Zhang H., Owen T., et al. Production of RANKL by memory B cells: a link between B cells and bone erosion in rheumatoid arthritis. Arthritis & Rheumatology. 2016;68(4):805–816. doi: 10.1002/art.39489. - DOI - PMC - PubMed
    1. Horváth Á., Pusztai A., Gulyás K., et al. A4.3 Effects of anti-TNF therapy on markers of bone homeostasis in rheumatoid arthritis and ankylosing spondylitis. Annals of the Rheumatic Diseases. 2015;74(2, article A37) doi: 10.1136/annrheumdis-2015-207259.85. - DOI
    1. Fadda S., Hamdy A., Abulkhair E., Mahmoud Elsify H., Mostafa A. Serum levels of osteoprotegerin and RANKL in patients with rheumatoid arthritis and their relation to bone mineral density and disease activity. The Egyptian Rheumatologist. 2015;37(1):1–6. doi: 10.1016/j.ejr.2014.06.001. - DOI

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