Mar 14, 2020

RNA sequencing reveals interacting key determinants of osteoarthritis acting in subchondral bone and articular cartilage.

Margo TuerlingsIngrid Meulenbelt


Objective: The aim of this study was to identify key determinants of the interactive osteoarthritis (OA) pathophysiological processes of subchondral bone and cartilage. Methods: We performed RNA sequencing on macroscopically preserved and lesioned OA subchondral bone of patients that underwent joint replacement surgery due to OA (N=24 pairs; 6 hips, 18 knees, RAAK-study). Unsupervised hierarchical clustering and differential expression analyses were performed. Results were combined with previously identified, differentially expressed genes in cartilage (partly overlapping samples) as well as with recently identified OA risk genes. Results: We identified 1569 genes significantly differentially expressed between lesioned and preserved subchondral bone, including CNTNAP2 (FC=2.4, FDR=3.36x10-5) and STMN2 (FC=9.6, FDR=3.36x10-3). Among the identified genes, 305 were also differentially expressed and with same direction of effects in cartilage, including IL11 and CHADL , recently acknowledged OA susceptibility genes. Upon differential expression analysis stratifying for joint site, we identified 509 genes exclusively differentially expressed in subchondral bone of the knee, such as KLF11 and WNT4 . These exclusive knee genes were en...Continue Reading

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Mentioned in this Paper

Epigenetic Process
WNT4 protein, human
CNTNAP2 protein, human
STMN2 protein, human
Degenerative Polyarthritis

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