Col9a2 gene deletion accelerates the degeneration of intervertebral discs

As an essential component of the extracellular matrix (ECM) in cartilage, the a2 chain of type IX collagen (Col9a2), has been implicated in human intervertebral disc degeneration (IVDD). However, the precise role of the Col9a2 gene in the pathogenesis of IVDD has remained elusive. In the present stu...

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Published in:Experimental and therapeutic medicine 2022-03, Vol.23 (3), Article 207
Main Authors: Xu, Huihui, Dong, Rui, Zeng, Qinghe, Fang, Liang, Ge, Qinwen, Xia, Chenjie, Zhang, Peng, Lv, Shuaijie, Zou, Zhen, Wang, Pinger, Li, Ju, Ruan, Hongfeng, Hu, Songfeng, Wu, Chengliang, Jin, Hongting, Tong, Peijian
Format: Article
Language:English
Subjects:
Bone marrow
Cartilage
Chromosome deletion
Collagen
Degeneration (Pathology)
Dilution
Genetic aspects
Health aspects
Intervertebral disk
Laboratory animals
Nutrition
Pain
Permeability
Physiological aspects
Spinal diseases
Statistical analysis
Vertebrae
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Summary:As an essential component of the extracellular matrix (ECM) in cartilage, the a2 chain of type IX collagen (Col9a2), has been implicated in human intervertebral disc degeneration (IVDD). However, the precise role of the Col9a2 gene in the pathogenesis of IVDD has remained elusive. In the present study, the spines of Col9a2-deficient ([Col9a2.sup.-/-]) mice were systematically analyzed and compared with wild-type control mice using micro-CT ([micro]CT), histomorphology, immunofluorescence, immunohistochemistry and reverse transcription-quantitative PCR (RT-qPCR). [micro]CT analysis revealed that endplate (EP) osteochondral remodeling in the [Col9a2.sup.-/-] group was accompanied by a significant increase in EP porosity. Likewise, histopathological staining at 12 weeks revealed that the [Col9a2.sup.-/-] mice exhibited a marked early-stage IVDD phenotype, including EP sclerosis, calcification and annulus fibrosus rupture. The immunofluorescence results indicated that Col9a2 was extensively expressed in the IVDs, whereas it was barely detectable in [Col9a2.sup.-/-] mice. Immunohistochemical and RT-qPCR analyses demonstrated that the expression levels of Col2a1 and Aggrecan in the IVDs of [Col9a2.sup.-/-] mice were significantly decreased. In addition, the levels of Mmp13, ADAM metallopeptidase with thrombospondin type 1 motif 5, Col10a1 and Runx family transcription factor 2 were significantly elevated. These results suggested that deletion of the Col9a2 gene led to osteochondral remodeling of cartilage EP and suppressed ECM synthesis, accelerating matrix degradation and chondrocyte hypertrophy in the IVD tissue. Key words: Col9a2, endplate, calcification, ossification, intervertebral disc degeneration
ISSN:1792-0981
1792-1015
DOI:10.3892/etm.2022.11130