期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 75, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2019.105752
关键词
Histone deacetylase 4; Rat chondrocyte; Anterior cruciate ligament transection (ACLT); Osteoarthritis (OA); Adenovirus vector
资金
- National Natural Science Foundation of China [81772415]
- National Science Foundation for Young Scientists of China [81601949]
- National International Science and Technology Cooperation Project [2015DFA33050]
- Osteoarthritis Biological Sample Resource Sharing Service Platform Construction Project of Shanxi Province [201705D121010]
Background: Downregulation of histone deacetylase-4 (HDAC4) contributes to cartilage degeneration in osteoarthritis (OA) because it promotes upregulation of runt-related transcription factor-2 (Runx-2) and osteoarthritis-related genes. The effect of HDAC4 upregulation on cartilage damage in OA remains unknown. Methods: Rat chondrocytes were infected with Ad-GFP or Ad-HDAC4-GFP for 48 h, stimulated with interleukin-1 beta (IL-1 beta, 10 ng/mL) for 24 h, and then harvested for RT-qPCR. Male Sprague-Dawley rats in 3 groups were given anterior cruciate ligament transection (ACLT) or sham operation, and knee injections with different adenovirus (Ad) vectors at 48 h after surgery and every 3 weeks thereafter: ACLT+ Ad-GFP (n = 17); ACLT + Ad-HDAC4-GFP (n = 20); and sham + Ad-GFP (n = 15). Three ACLT-Ad-HDAC4-GFP rats were sacrificed at different times to examine the expression of HDAC4. Two ACLT-Ad-GFP rats and two ACLT-Ad-HDAC4-GFP rats were euthanized at week-2; articular cartilage was harvested and expression of HDAC4 was determined by RT-qPCR. All other rats were euthanized at week-8. Cartilage damage and OA progression was assessed using radiography, fluorescence molecular tomography (FMT), histology, immunohistochemistry (IHC), ELISA, and RT-qPCR. Results: Overexpression of HDAC4 in chondrocytes stimulated by IL-1 beta reduced the levels of Runx-2, MMP-13, and Collagen X, but increased the levels of Collagen II and Aggrecan. Upregulation of HDAC4 reduced osteophyte formation and cartilage damage, and increased articular cartilage anabolism. Conclusion: HDAC4 attenuated articular cartilage damage by repression of Runx-2, MMP-13, and collagen X and induction of collagen II and ACAN in this rat model of OA. Upregulation of HDAC4 may provide chondroprotection in OA patients.
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