Background: Autologous chondrocyte implantation (ACI) requires a large number of
human hyaline chondrocytes. Unfortunately, human hyaline chondrocytes often
undergo dedifferentiation in vitro. Long non-coding RNAs (lncRNA) play a
regulatory role in gene expression in many pathological and physiological processes.
However, their role in human hyaline chondrocyte dedifferentiation remains unclear.
This study aimed to investigate the expression profiles of lncRNAs in human hyaline
chondrocyte dedifferentiation.
Methods: Human hyaline chondrocytes were cultured in vitro and screened for the
occurrence of dedifferentiation using real-time quantitative PCR (qPCR),
immunofluorescence, and western blotting. The expression profiles of lncRNAs and
mRNAs during dedifferentiation were analyzed by microarray analysis and real-time
qPCR. We used pellet culture to redifferentiate chondrocytes and the expression of
related lncRNAs were assessed. The function of lncRNA AP001505.9
(ENST00000569966) was determined by overexpression, fluorescence in situ
hybridization, competing endogenous RNA (ceRNA) analysis, and double luciferase
labeling.
Results: We probed human hyaline chondrocytes dedifferentiation and identified 334
upregulated and 381 downregulated lncRNAs. The expression of downregulated
lncRNA AP001505.9 in dedifferentiation was reversed by pellet culture. The
overexpression of AP001505.9 inhibited dedifferentiation by promoting the
expression of SRY-Box transcription factor 9 (SOX-9) and inhibiting the expression
of type I collagen (COL1) both in vitro and in vivo.
Conclusion: This study reveals for the first time the expression profiles of lncRNAs
in human hyaline chondrocyte dedifferentiation, thereby providing a new perspective
for exploring the potential mechanism of chondrocyte dedifferentiation.