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Inhibition of HOXD11 promotes cartilage degradation and induces osteoarthritis development.
- Source :
- Journal of Orthopaedic Surgery & Research; 2/2/2024, Vol. 19 Issue 1, p1-12, 12p
- Publication Year :
- 2024
-
Abstract
- The 5′-HOXD genes are important for chondrogenesis in vertebrates, but their roles in osteoarthritis (OA) are still ambiguous. In our study, 5′-HOXD genes involvement contributing to cartilage degradation and OA was investigated. In bioinformatics analysis of 5′-HOXD genes, we obtained the GSE169077 data set related to OA in the GEO and analyzed DEGs using the GEO2R tool attached to the GEO. Then, we screened the mRNA levels of 5′-HOXD genes by quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR). We discovered that OA chondrocyte proliferation was inhibited, and apoptosis was increased. Moreover, it was discovered that SOX9 and COL2A1 were downregulated at mRNA and protein levels, while matrix metalloproteinases (MMPs) and a disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTSs) were upregulated. According to the results of differentially expressed genes (DEGs) and qRT-PCR, we evaluated the protein level of HOXD11 and found that the expression of HOXD11 was downregulated, reversed to MMPs and ADAMTSs but consistent with the cartilage-specific factors, SOX9 and COL2A1. In the lentivirus transfection experiments, HOXD11 overexpression reversed the effects in OA chondrocytes. In human OA articular cartilage, aberrant subchondral bone was formed in hematoxylin–eosin (H&E) and Safranin O and fast green (SOFG) staining results. Furthermore, according to immunohistochemistry findings, SOX9 and HOXD11 expression was inhibited. The results of this study established that HOXD11 was downregulated in OA cartilage and that overexpression of HOXD11 could prevent cartilage degradation in OA. [ABSTRACT FROM AUTHOR]
- Subjects :
- PROTEINS
BIOLOGICAL models
KNEE osteoarthritis
CARTILAGE cells
DISEASE progression
REVERSE transcriptase polymerase chain reaction
STAINS & staining (Microscopy)
ANIMAL experimentation
IMMUNOHISTOCHEMISTRY
CARTILAGE diseases
MATRIX metalloproteinases
OSTEOARTHRITIS
MESSENGER RNA
CELL proliferation
DESCRIPTIVE statistics
RESEARCH funding
ARTICULAR cartilage
TRANSCRIPTION factors
MICE
CHEMICAL inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1749799X
- Volume :
- 19
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Journal of Orthopaedic Surgery & Research
- Publication Type :
- Academic Journal
- Accession number :
- 175232342
- Full Text :
- https://doi.org/10.1186/s13018-024-04573-7