Item Infomation
Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor | Baron, Dr. Roland | - |
| dc.contributor | Kawai, Dr. Toshi | - |
| dc.contributor | Howell, Dr. Howard | - |
| dc.contributor | Whitman, Dr. Malcolm | - |
| dc.creator | Khoynezhad, Shirin | - |
| dc.date | 2015-07-14T19:09:04Z | - |
| dc.date | 2015-05 | - |
| dc.date | 2015-07-02 | - |
| dc.date | 2015 | - |
| dc.date | 2015-07-14T19:09:04Z | - |
| dc.date.accessioned | 2023-04-10T04:30:25Z | - |
| dc.date.available | 2023-04-10T04:30:25Z | - |
| dc.identifier | Khoynezhad, Shirin. 2015. Halofuginone Prevents the Progression of Osteoarthritis. Doctoral dissertation, Harvard School of Dental Medicine. | - |
| dc.identifier | http://nrs.harvard.edu/urn-3:HUL.InstRepos:17331948 | - |
| dc.identifier.uri | http://lib.yhn.edu.vn/handle/YHN/172 | - |
| dc.description | Background: Halofuginone (HF) is a natural product that has been shown to have therapeutic benefits in a variety of pathologic conditions, from cancer to autoimmune diseases. These beneficial effects are mainly through inhibition of pro-inflammatory cytokines. Inflammatory cytokines have been recently shown to exert a crucial role in development of osteoarthritis and one of their most important targets is Matrix metallopeptidase-13 (MMP-13). In this preclinical study, we investigated the effect of HF on the progression of Osteoarthritis. Methods: The effect of adding HF ± IL-1β/TNF-α on mRNA expression of MMP-13 on the C28/I2 Chondrocytes was evaluated with qPCR in vitro. To study the effect of HF in vivo, a mice destabilization of the medial meniscus (DMM) osteoarthritis model was employed and untreated control group were compared with early treatment with HF (starting 48 hours post-surgery for 12 weeks) and late treatment (4 weeks post-surgery for 8 weeks). After sacrificing the animal, joint destruction in the knee tissue was assessed with Safranine O/Fast Green staining and MMP13 expression was evaluated by immunohistochemical staining. Results: In chondrocytes, MMP-13 expression was significantly increased with IL-1β or TNF-α (13.77-fold, p-value<0.05 and 5.8-fold, p-value<0.05, respectively). Addition of HF Significantly reduced MMP13 expression close to baseline levels (1.73-fold, p-value<0.05 when co-incubated with IL-1β and 1.6-fold p-value<0.05 when co-incubated with TNF-α). Injection of HF in the mice osteoarthritis model in vivo, significantly reduced Osteoarthritis progression according to OARSI scoring (3.8 vs. 1.16 vs. 1.07, p-value<0.05) and there was no difference between early vs. late administration of HF. While MMP-13 was overexpressed in the control (DMM surgery without HF treatment) groups in IHC staining, expression of MMP13 was suppressed by injection of HF in both groups. Conclusion: Halofuginone inhibits MMP-13 expression and diminishes joint destruction. These preclinical findings provide supporting data for clinical investigation of HF as a therapeutic target for osteoarthritis. | - |
| dc.description | Osteoarthritis, Halofuginone, MMP-13, Knee Joint, TMJ | - |
| dc.format | application/pdf | - |
| dc.format | application/pdf | - |
| dc.language | en | - |
| dc.subject | Biology, Molecular | - |
| dc.subject | Health Sciences, Pharmacology | - |
| dc.title | Halofuginone Prevents the Progression of Osteoarthritis | - |
| dc.type | Thesis or Dissertation | - |
| dc.type | text | - |
| Appears in Collections | Y học | |
Files in This Item:
