SNORC knockdown alleviates inflammation, autophagy defect and matrix degradation of chondrocytes in osteoarthritis development.

Publisher: Springer Country of Publication: Netherlands NLM ID: 0364456 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-4919 (Electronic) Linking ISSN: 03008177 NLM ISO Abbreviation: Mol Cell Biochem Subsets: MEDLINE

Publication: New York : Springer
Original Publication: The Hague, Dr. W. Junk B. V. Publishers.

Chondrocytes*/metabolism ; Chondrocytes*/pathology ; Autophagy* ; Osteoarthritis*/metabolism ; Osteoarthritis*/pathology ; Osteoarthritis*/genetics ; Inflammation*/metabolism ; Inflammation*/pathology; Animals ; Rats ; Rats, Sprague-Dawley ; Male ; Interleukin-1beta/metabolism ; Gene Knockdown Techniques ; Extracellular Matrix/metabolism ; MAP Kinase Signaling System

Excessive inflammation and autophagy defect of chondrocytes play important roles in the pathological process of osteoarthritis (OA). The present study aimed to clarify the roles of small novel rich in cartilage (SNORC) in these pathological changes of chondrocytes in OA. Bioinformatics analysis of GEO dataset GSE207881 displayed that SNORC was a potential biomarker for OA. As confirmed by quantitative real-time PCR, immunohistochemical staining and western blotting, SNORC was significantly up-regulated in cartilage of OA rat model and interleukin (IL)-1β-stimulated primary rat articular chondrocytes in contrast to their corresponding normal control. Knocking down SNORC in IL-1β-induced chondrocytes obviously suppressed the production of nitric oxide (NO), IL-6, tumor necrosis factor (TNF)-α and prostaglandin E2 (PGE2) to alleviate inflammation, and reduced the protein levels of a disintegrin and metalloproteinase with thrombospondin 5 (ADAMTS5) and matrix metallopeptidase (MMP)13 and elevated collagen type 2 alpha 1 (COL2A1) level to improve matrix degradation. Down-regulation of SNORC increased Beclin1 expression and LC3II/LC3I ratio, but suppressed p62 expression to restore impaired autophagy in IL-1β-induced chondrocytes. Moreover, down-regulating SNORC mitigated mitochondrial dysfunction and apoptosis in IL-1β-stimulated chondrocytes. Mechanically, SNORC simultaneously activated the phosphatidylinositol-3-kinase/serine threonine kinase (PI3K/AKT) and c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway in the IL-1β-induced chondrocyte, while re-activating the PI3K and JNK signals abolished the suppressive effect of down-regulating SNORC on IL-1β-induced chondrocyte damage. In a word, SNORC knockdown alleviates inflammation, matrix degradation, autophagy defect and excessive apoptosis of chondrocytes during OA development via suppressing the PI3K and JNK signaling pathway.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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Grant No. ZX20191001 the Yunnan Traumatology and Orthopedics Clinical Medical Center; Grant No. 202102AA310068 the Grants from Yunnan Orthopedics and Sports Rehabilitation Clinical Medicine Research Center; Grant No. 202005AD160146 Technical Innovation Talents Training Object Project

Keywords: Autophagy; Chondrocytes; Extracellular matrix degradation; Osteoarthritis; Small novel rich in cartilage

0 (Interleukin-1beta)

Date Created: 20230902 Date Completed: 20240903 Latest Revision: 20240903

20240903

10.1007/s11010-023-04842-9

37659033