J Bone Metab.  2014 Nov;21(4):249-255. 10.11005/jbm.2014.21.4.249.

Effect of Zoledronate on the Expression of Vascular Endothelial Growth Factor-A by Articular Chondrocytes and Synovial Cells: An in Vitro Study

Affiliations
  • 1Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Korea.
  • 2Department of Orthopedic Surgery, Yonsei University Gangnam Severance Hospital, Seoul, Korea. wsleeos@yuhs.ac
  • 3Department of Orthopedic Surgery, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea.

Abstract

BACKGROUND
The aim of this in vitro study was to determine the effect of zoledronate, which is frequently used to treat osteoporosis, on osteoarthritis by analyzing zoledronate-induced expression of vascular endothelial growth factor-A (VEGF-A) in chondrocytes and synovial cells.
METHODS
After chondrocytes and synovial cells were separated and cultured, zoledronate was added, and VEGF-A and pigment epithelium-derived factor (PEDF) expression were quantified by real-time polymerase chain reaction and Western blotting.
RESULTS
There was no significant difference in the expression of VEGF-A mRNA in chondrocytes between the zoledronate group and the control group on the 8th day of culture. The expression of both VEGF-A and PEDF mRNA in synovial cells was significantly decreased in the zoledronate group (P<0.05).
CONCLUSIONS
Zoledronate decreases the expression of VEGF-A in synovial cells and may affect the development and progression of osteoarthritis.

Keyword

Chondrocytes; Osteoarthritis; Synovial cells; Vascular endothelial growth factor-A; Zoledronate

MeSH Terms

Blotting, Western
Chondrocytes*
Osteoarthritis
Osteoporosis
Real-Time Polymerase Chain Reaction
RNA, Messenger
Vascular Endothelial Growth Factor A*
RNA, Messenger
Vascular Endothelial Growth Factor A

Figure

  • Fig. 1 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results after culture of chondrocytes in scaffolds for 3, 5, and 8 days. Significant differences are found in the 10-5 mol/L and 10-4 mol/L groups of zoledronate (P<0.001).

  • Fig. 2 Proliferation of chondrocytes. Cell number increased in cells treated with 10-7 mol/L zoledronate relative to the control group by day 3, but this difference was not significant for each time point (P>0.05).

  • Fig. 3 Proliferation of synovial cells. Cell number decreased in cells treated with 10-7 mol/L zoledronate relative to the control group by day 8, but this difference was not significant for each time point (P>0.05).

  • Fig. 4 Expression of vascular endothelial growth factor-A (VEGF-A) mRNA in zoledronate-treated chondrocytes was lower than in the control group at day 8, but this difference was not significant (P=0.155). ZA, zoledronate.

  • Fig. 5 Expression of pigment epithelium-derived factor (PEDF) mRNA in zoledronate-treated chondrocytes was lower than in the control group at day 8, but this difference was not significant (P=0.631). ZA, zoledronate.

  • Fig. 6 Expression of vascular endothelial growth factor-A (VEGF-A) mRNA in zoledronate-treated synovial cells was significantly lower than in the control group at day 8 (*P=0.022). ZA, zoledronate.

  • Fig. 7 Expression of pigment epithelium-derived factor (PEDF) mRNA in zoledronate-treated synovial cells was significantly lower than in the control group at day 8 (*P=0.041). ZA, zoledronate.

  • Fig. 8 Western blot analysis for vascular endothelial growth factor (VEGF) & pigment epithelium-derived factor (PEDF) in chondrocytes and synovial cells with or without zoledronate revealed no significant difference in chondrocytes, but a significant difference in synovial cells (P=0.039, P=0.020). VEGF, vascular endothelial growth factor; PEDF, pigment epithelium-derived factor; ZA, zoledronate.


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