Purpose
To determine the role of histone deacetylase 4 (HDAC4)-controlled chondrocyte hypertrophy in the onset and development of age-related osteoarthritis (OA).
Methods
Morphological analysis of human knee cartilages was performed to observe structural changes during cartilage degeneration. HDAC4 expression was deleted in adult aggrecan (Acan)-CreERT2; HDAC4fl/fl transgenic mice. The onset and development of age-related OA were investigated in transgenic and control mice using hematoxylin and eosin (H&E) and Safranin O staining. Furthermore, the progression of ACLT-induced OA following adenovirus-mediated HDAC4 overexpression was explored in rats. The expression levels of genes related to hypertrophy, cartilage matrix and its digestion, and chondrocyte proliferation were investigated using qPCR. Immunohistochemistry (IHC) was used to explore the mechanisms underlying HDAC4-controlled age-related changes in OA progression.
Results
In human cartilage, we performed morphological analysis and IHC, the results showed that hypertrophy-related structural changes are related to HDAC4 expression. Age-related OA was detected early (OARSI scores 2.7 at 8-month-old) following HDAC4 deletion in 2-month-old mice. Furthermore, qPCR and IHC results showed changes in hypertrophy-related genes Col10a1, Runx2 and Sox9 in chondrocytes, particularly in the expression of Runt-related transcription factor 2 (Runx2, 13.29±0.99 fold). The expression of the main cartilage matrix-related genes Col2a1 and Acan decreased, that of cartilage matrix digestion-related gene MMP-13 increased, while that of chondrocyte proliferation-related genes PTHrP, Ihh and Gli1 changed. In contrast, rat cartilage’s qPCR and IHC results showed opposite outcomes after HDAC4 overexpression.
Conclusion
Based on the results above, we concluded that HDAC4 expression regulates the onset and development of age-related OA by controlling chondrocyte hypertrophy. These results may help in the development of early diagnosis and treatment of age-related OA.
Both William Wordsworth and Wang Wei are prominent idyllic poets who chanted nature and sought beauty and divinity from nature. While sharing similarities, they contrasted each other in many respects in their poetic works. Wang Wei's poems were deeply influenced by Zen Buddhism, which gave nature a rich connotation in addition to the idea of "unity of heaven and man". William Wordsworth, greatly affected by pantheism, resorted to poetry to explore philosophical issues in life like the relationship between nature, man and divinity of the Heaven. In the current era, the process of economic development and the continuous integration of different societies and civilizations are still full of contradictions. Thinking, deepening and adjusting the relationship between man and nature is to maintain harmony between man and nature, so as to arrive at the destination of promoting economic development and social progress. This article focuses on the similarities and differences between William Wordsworth and Wang Wei as well as their works, analyzes the causes, and then reveals the significance and insight, in order to provide constructive references to build a modern harmonious society.
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